ES2372229T3 - Modelos de selección in vivo para el tratamiento de la enfermedad de alzheimer y otros trastornos relacionados con qpct. - Google Patents
Modelos de selección in vivo para el tratamiento de la enfermedad de alzheimer y otros trastornos relacionados con qpct. Download PDFInfo
- Publication number
- ES2372229T3 ES2372229T3 ES08707977T ES08707977T ES2372229T3 ES 2372229 T3 ES2372229 T3 ES 2372229T3 ES 08707977 T ES08707977 T ES 08707977T ES 08707977 T ES08707977 T ES 08707977T ES 2372229 T3 ES2372229 T3 ES 2372229T3
- Authority
- ES
- Spain
- Prior art keywords
- glutaminyl cyclase
- dna
- transgene
- mouse
- human
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 22
- 208000024827 Alzheimer disease Diseases 0.000 title description 24
- 230000009261 transgenic effect Effects 0.000 claims abstract description 123
- 108700019146 Transgenes Proteins 0.000 claims abstract description 57
- 238000000034 method Methods 0.000 claims abstract description 46
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 45
- 238000011830 transgenic mouse model Methods 0.000 claims abstract description 30
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 22
- 108010081484 glutaminyl-peptide cyclotransferase Proteins 0.000 claims description 105
- 102000003642 glutaminyl-peptide cyclotransferase Human genes 0.000 claims description 104
- 230000000694 effects Effects 0.000 claims description 102
- 241001465754 Metazoa Species 0.000 claims description 80
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 55
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 52
- 238000012360 testing method Methods 0.000 claims description 35
- 101000585315 Homo sapiens Glutaminyl-peptide cyclotransferase Proteins 0.000 claims description 28
- 239000012634 fragment Substances 0.000 claims description 25
- 229920001184 polypeptide Polymers 0.000 claims description 23
- 241001529936 Murinae Species 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 16
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- 239000002773 nucleotide Substances 0.000 claims description 14
- 125000003729 nucleotide group Chemical group 0.000 claims description 14
- 238000001727 in vivo Methods 0.000 claims description 12
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 claims description 11
- 229940124597 therapeutic agent Drugs 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 108010044467 Isoenzymes Proteins 0.000 claims description 6
- 239000013543 active substance Substances 0.000 claims description 3
- 230000000926 neurological effect Effects 0.000 claims description 3
- 101710095468 Cyclase Proteins 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 229940123320 Cyclase inhibitor Drugs 0.000 claims 1
- 108700039855 mouse a Proteins 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract description 16
- 239000000203 mixture Substances 0.000 abstract description 15
- 108020004414 DNA Proteins 0.000 description 103
- 210000004027 cell Anatomy 0.000 description 74
- 230000014509 gene expression Effects 0.000 description 57
- 239000013615 primer Substances 0.000 description 56
- 238000006243 chemical reaction Methods 0.000 description 40
- 102000004190 Enzymes Human genes 0.000 description 39
- 108090000790 Enzymes Proteins 0.000 description 39
- 229940088598 enzyme Drugs 0.000 description 39
- 210000001519 tissue Anatomy 0.000 description 34
- 239000013598 vector Substances 0.000 description 31
- 239000002299 complementary DNA Substances 0.000 description 29
- 239000013612 plasmid Substances 0.000 description 29
- 210000004556 brain Anatomy 0.000 description 26
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 24
- 241000699660 Mus musculus Species 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000012636 effector Substances 0.000 description 21
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 20
- 230000002255 enzymatic effect Effects 0.000 description 20
- 239000003112 inhibitor Substances 0.000 description 20
- 238000007363 ring formation reaction Methods 0.000 description 20
- 239000000758 substrate Substances 0.000 description 20
- 150000001413 amino acids Chemical class 0.000 description 18
- 235000018102 proteins Nutrition 0.000 description 18
- 239000000523 sample Substances 0.000 description 17
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 16
- 241000699666 Mus <mouse, genus> Species 0.000 description 16
- 241000699670 Mus sp. Species 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 15
- 210000002569 neuron Anatomy 0.000 description 15
- 229910001868 water Inorganic materials 0.000 description 15
- 238000005755 formation reaction Methods 0.000 description 14
- 239000003550 marker Substances 0.000 description 14
- 238000000520 microinjection Methods 0.000 description 14
- 150000007523 nucleic acids Chemical group 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 230000001105 regulatory effect Effects 0.000 description 14
- 241000124008 Mammalia Species 0.000 description 13
- 230000033228 biological regulation Effects 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 206010012289 Dementia Diseases 0.000 description 12
- 239000007983 Tris buffer Substances 0.000 description 12
- 238000000338 in vitro Methods 0.000 description 12
- 210000002381 plasma Anatomy 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 12
- 210000004185 liver Anatomy 0.000 description 11
- 108020004999 messenger RNA Proteins 0.000 description 11
- 102000039446 nucleic acids Human genes 0.000 description 11
- 108020004707 nucleic acids Proteins 0.000 description 11
- 108020001019 DNA Primers Proteins 0.000 description 10
- 239000003155 DNA primer Substances 0.000 description 10
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 10
- 235000001014 amino acid Nutrition 0.000 description 10
- 229940024606 amino acid Drugs 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 239000000872 buffer Substances 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 238000005259 measurement Methods 0.000 description 10
- 210000000287 oocyte Anatomy 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 9
- 102400001103 Neurotensin Human genes 0.000 description 9
- 101800001814 Neurotensin Proteins 0.000 description 9
- 238000000855 fermentation Methods 0.000 description 9
- 230000004151 fermentation Effects 0.000 description 9
- 238000003205 genotyping method Methods 0.000 description 9
- 229930195712 glutamate Natural products 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 230000010354 integration Effects 0.000 description 9
- 210000003734 kidney Anatomy 0.000 description 9
- 229910052751 metal Inorganic materials 0.000 description 9
- 239000002184 metal Substances 0.000 description 9
- 230000004048 modification Effects 0.000 description 9
- 238000012986 modification Methods 0.000 description 9
- PCJGZPGTCUMMOT-ISULXFBGSA-N neurotensin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 PCJGZPGTCUMMOT-ISULXFBGSA-N 0.000 description 9
- 108700021111 pyroglutamyl-glutamyl-proline amide Proteins 0.000 description 9
- JBIJLHTVPXGSAM-UHFFFAOYSA-N 2-naphthylamine Chemical compound C1=CC=CC2=CC(N)=CC=C21 JBIJLHTVPXGSAM-UHFFFAOYSA-N 0.000 description 8
- 201000010374 Down Syndrome Diseases 0.000 description 8
- HYZBGWLLSXSYLX-GUBZILKMSA-N Pglu-glu-pro-amide Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(O)=O)NC(=O)[C@H]1NC(=O)CC1 HYZBGWLLSXSYLX-GUBZILKMSA-N 0.000 description 8
- 238000007792 addition Methods 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 210000001671 embryonic stem cell Anatomy 0.000 description 8
- 210000002257 embryonic structure Anatomy 0.000 description 8
- 230000004927 fusion Effects 0.000 description 8
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 8
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 108091033319 polynucleotide Proteins 0.000 description 8
- 102000040430 polynucleotide Human genes 0.000 description 8
- 239000002157 polynucleotide Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- 239000006228 supernatant Substances 0.000 description 8
- 235000009467 Carica papaya Nutrition 0.000 description 7
- 241000235058 Komagataella pastoris Species 0.000 description 7
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 7
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 7
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 7
- 235000011130 ammonium sulphate Nutrition 0.000 description 7
- 235000011187 glycerol Nutrition 0.000 description 7
- 238000009396 hybridization Methods 0.000 description 7
- 239000008363 phosphate buffer Substances 0.000 description 7
- 239000002243 precursor Substances 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 208000037259 Amyloid Plaque Diseases 0.000 description 6
- 241000196324 Embryophyta Species 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 108700026244 Open Reading Frames Proteins 0.000 description 6
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 6
- 210000005013 brain tissue Anatomy 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 6
- 238000010367 cloning Methods 0.000 description 6
- 238000004925 denaturation Methods 0.000 description 6
- 230000036425 denaturation Effects 0.000 description 6
- 230000001419 dependent effect Effects 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 239000006167 equilibration buffer Substances 0.000 description 6
- 230000035558 fertility Effects 0.000 description 6
- 230000002068 genetic effect Effects 0.000 description 6
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 6
- 210000001161 mammalian embryo Anatomy 0.000 description 6
- 239000013642 negative control Substances 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 230000002441 reversible effect Effects 0.000 description 6
- 241000219173 Carica Species 0.000 description 5
- 240000006432 Carica papaya Species 0.000 description 5
- 208000023105 Huntington disease Diseases 0.000 description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 5
- 101150052863 THY1 gene Proteins 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 208000010877 cognitive disease Diseases 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003623 enhancer Substances 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 230000001939 inductive effect Effects 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 208000027061 mild cognitive impairment Diseases 0.000 description 5
- 230000004770 neurodegeneration Effects 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 229940043131 pyroglutamate Drugs 0.000 description 5
- 238000003753 real-time PCR Methods 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 238000012163 sequencing technique Methods 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 230000009466 transformation Effects 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 102000004400 Aminopeptidases Human genes 0.000 description 4
- 108090000915 Aminopeptidases Proteins 0.000 description 4
- 241000283690 Bos taurus Species 0.000 description 4
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
- XNSAINXGIQZQOO-UHFFFAOYSA-N L-pyroglutamyl-L-histidyl-L-proline amide Natural products NC(=O)C1CCCN1C(=O)C(NC(=O)C1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-UHFFFAOYSA-N 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 4
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 4
- 239000000627 Thyrotropin-Releasing Hormone Substances 0.000 description 4
- 101800004623 Thyrotropin-releasing hormone Proteins 0.000 description 4
- 102400000336 Thyrotropin-releasing hormone Human genes 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 238000009825 accumulation Methods 0.000 description 4
- 239000012190 activator Substances 0.000 description 4
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 4
- 239000000164 antipsychotic agent Substances 0.000 description 4
- 238000009395 breeding Methods 0.000 description 4
- 230000001488 breeding effect Effects 0.000 description 4
- 238000006555 catalytic reaction Methods 0.000 description 4
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 238000004520 electroporation Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 210000004602 germ cell Anatomy 0.000 description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 4
- 235000013922 glutamic acid Nutrition 0.000 description 4
- 239000004220 glutamic acid Substances 0.000 description 4
- 230000003054 hormonal effect Effects 0.000 description 4
- 208000000509 infertility Diseases 0.000 description 4
- 230000036512 infertility Effects 0.000 description 4
- 208000021267 infertility disease Diseases 0.000 description 4
- 239000004816 latex Substances 0.000 description 4
- 229920000126 latex Polymers 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 230000005012 migration Effects 0.000 description 4
- 238000013508 migration Methods 0.000 description 4
- 230000002018 overexpression Effects 0.000 description 4
- XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 4
- 239000011535 reaction buffer Substances 0.000 description 4
- 201000000980 schizophrenia Diseases 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 229940034199 thyrotropin-releasing hormone Drugs 0.000 description 4
- 238000011820 transgenic animal model Methods 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 238000000108 ultra-filtration Methods 0.000 description 4
- 241001430294 unidentified retrovirus Species 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- 208000030507 AIDS Diseases 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 3
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 3
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 3
- 241000701022 Cytomegalovirus Species 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102100029846 Glutaminyl-peptide cyclotransferase Human genes 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 238000010268 HPLC based assay Methods 0.000 description 3
- 206010019375 Helicobacter infections Diseases 0.000 description 3
- 241000238631 Hexapoda Species 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 239000007993 MOPS buffer Substances 0.000 description 3
- 241000282567 Macaca fascicularis Species 0.000 description 3
- 241000282560 Macaca mulatta Species 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 208000028017 Psychotic disease Diseases 0.000 description 3
- 238000011529 RT qPCR Methods 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 206010038997 Retroviral infections Diseases 0.000 description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 description 3
- 206010052779 Transplant rejections Diseases 0.000 description 3
- 208000025865 Ulcer Diseases 0.000 description 3
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 229960005305 adenosine Drugs 0.000 description 3
- 102000030621 adenylate cyclase Human genes 0.000 description 3
- 108060000200 adenylate cyclase Proteins 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 3
- 230000037424 autonomic function Effects 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000003542 behavioural effect Effects 0.000 description 3
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 3
- 210000001124 body fluid Anatomy 0.000 description 3
- 239000010839 body fluid Substances 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 208000019425 cirrhosis of liver Diseases 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 235000013601 eggs Nutrition 0.000 description 3
- 210000003038 endothelium Anatomy 0.000 description 3
- 230000037149 energy metabolism Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000007850 fluorescent dye Substances 0.000 description 3
- 230000037406 food intake Effects 0.000 description 3
- 235000012631 food intake Nutrition 0.000 description 3
- 206010017758 gastric cancer Diseases 0.000 description 3
- 230000003284 homeostatic effect Effects 0.000 description 3
- 230000028709 inflammatory response Effects 0.000 description 3
- 230000021633 leukocyte mediated immunity Effects 0.000 description 3
- 210000005228 liver tissue Anatomy 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 239000006166 lysate Substances 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 230000009826 neoplastic cell growth Effects 0.000 description 3
- 210000004498 neuroglial cell Anatomy 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 230000000269 nucleophilic effect Effects 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 230000035790 physiological processes and functions Effects 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 208000005069 pulmonary fibrosis Diseases 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 201000002793 renal fibrosis Diseases 0.000 description 3
- 208000037803 restenosis Diseases 0.000 description 3
- 230000001177 retroviral effect Effects 0.000 description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- 239000007974 sodium acetate buffer Substances 0.000 description 3
- 201000011549 stomach cancer Diseases 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- YZJSUQQZGCHHNQ-BYPYZUCNSA-N (2s)-6-amino-2-azaniumyl-6-oxohexanoate Chemical compound OC(=O)[C@@H](N)CCCC(N)=O YZJSUQQZGCHHNQ-BYPYZUCNSA-N 0.000 description 2
- YPTJKHVBDCRKNF-UHFFFAOYSA-N 2',6'-Dihydroxyacetophenone Chemical compound CC(=O)C1=C(O)C=CC=C1O YPTJKHVBDCRKNF-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- 208000023697 ABri amyloidosis Diseases 0.000 description 2
- 208000018282 ACys amyloidosis Diseases 0.000 description 2
- 102400000345 Angiotensin-2 Human genes 0.000 description 2
- 101800000733 Angiotensin-2 Proteins 0.000 description 2
- 241001244729 Apalis Species 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 101000950981 Bacillus subtilis (strain 168) Catabolic NAD-specific glutamate dehydrogenase RocG Proteins 0.000 description 2
- 102100021257 Beta-secretase 1 Human genes 0.000 description 2
- 102000055006 Calcitonin Human genes 0.000 description 2
- 108060001064 Calcitonin Proteins 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 2
- 208000007487 Familial Cerebral Amyloid Angiopathy Diseases 0.000 description 2
- 102000016901 Glutamate dehydrogenase Human genes 0.000 description 2
- 102000005720 Glutathione transferase Human genes 0.000 description 2
- 108010070675 Glutathione transferase Proteins 0.000 description 2
- 208000032849 Hereditary cerebral hemorrhage with amyloidosis Diseases 0.000 description 2
- 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 description 2
- 101001129465 Homo sapiens Pyroglutamyl-peptidase 1 Proteins 0.000 description 2
- 201000000162 ITM2B-related cerebral amyloid angiopathy 1 Diseases 0.000 description 2
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 201000002832 Lewy body dementia Diseases 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 101000713102 Mus musculus C-C motif chemokine 1 Proteins 0.000 description 2
- 101000585320 Mus musculus Glutaminyl-peptide cyclotransferase Proteins 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 101100068676 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) gln-1 gene Proteins 0.000 description 2
- 206010029350 Neurotoxicity Diseases 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 101100124346 Photorhabdus laumondii subsp. laumondii (strain DSM 15139 / CIP 105565 / TT01) hisCD gene Proteins 0.000 description 2
- 206010062519 Poor quality sleep Diseases 0.000 description 2
- 102100031108 Pyroglutamyl-peptidase 1 Human genes 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- XYONNSVDNIRXKZ-UHFFFAOYSA-N S-methyl methanethiosulfonate Chemical compound CSS(C)(=O)=O XYONNSVDNIRXKZ-UHFFFAOYSA-N 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- 108010006785 Taq Polymerase Proteins 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 206010044221 Toxic encephalopathy Diseases 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 108010051583 Ventricular Myosins Proteins 0.000 description 2
- 108010084455 Zeocin Proteins 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- 230000009858 acid secretion Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 238000000246 agarose gel electrophoresis Methods 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- -1 amino-amino group Chemical group 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 206010002022 amyloidosis Diseases 0.000 description 2
- 229950006323 angiotensin ii Drugs 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 210000001130 astrocyte Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 210000002459 blastocyst Anatomy 0.000 description 2
- 210000001109 blastomere Anatomy 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 229960004015 calcitonin Drugs 0.000 description 2
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000013599 cloning vector Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- GNGACRATGGDKBX-UHFFFAOYSA-N dihydroxyacetone phosphate Chemical compound OCC(=O)COP(O)(O)=O GNGACRATGGDKBX-UHFFFAOYSA-N 0.000 description 2
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 210000002308 embryonic cell Anatomy 0.000 description 2
- 210000004188 enterochromaffin-like cell Anatomy 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 210000001156 gastric mucosa Anatomy 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 230000003862 health status Effects 0.000 description 2
- 101150113423 hisD gene Proteins 0.000 description 2
- 229960001340 histamine Drugs 0.000 description 2
- 238000001597 immobilized metal affinity chromatography Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 206010022498 insulinoma Diseases 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 230000013011 mating Effects 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 210000003643 myeloid progenitor cell Anatomy 0.000 description 2
- UPSFMJHZUCSEHU-JYGUBCOQSA-N n-[(2s,3r,4r,5s,6r)-2-[(2r,3s,4r,5r,6s)-5-acetamido-4-hydroxy-2-(hydroxymethyl)-6-(4-methyl-2-oxochromen-7-yl)oxyoxan-3-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](NC(C)=O)[C@H](OC=2C=C3OC(=O)C=C(C)C3=CC=2)O[C@@H]1CO UPSFMJHZUCSEHU-JYGUBCOQSA-N 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 230000007135 neurotoxicity Effects 0.000 description 2
- 231100000228 neurotoxicity Toxicity 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 244000039328 opportunistic pathogen Species 0.000 description 2
- 210000003101 oviduct Anatomy 0.000 description 2
- 210000001711 oxyntic cell Anatomy 0.000 description 2
- 208000021255 pancreatic insulinoma Diseases 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 2
- 230000001817 pituitary effect Effects 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 108010040003 polyglutamine Proteins 0.000 description 2
- 229920000155 polyglutamine Polymers 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000007859 qualitative PCR Methods 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 210000005084 renal tissue Anatomy 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 238000010187 selection method Methods 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 230000005062 synaptic transmission Effects 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000012549 training Methods 0.000 description 2
- 230000005026 transcription initiation Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
- VEPDWBJBPXVCEN-NSHDSACASA-N (2s)-2-amino-n-(4-methyl-2-oxochromen-7-yl)pentanediamide Chemical compound C1=C(NC(=O)[C@@H](N)CCC(N)=O)C=CC2=C1OC(=O)C=C2C VEPDWBJBPXVCEN-NSHDSACASA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- FGRBYDKOBBBPOI-UHFFFAOYSA-N 10,10-dioxo-2-[4-(N-phenylanilino)phenyl]thioxanthen-9-one Chemical compound O=C1c2ccccc2S(=O)(=O)c2ccc(cc12)-c1ccc(cc1)N(c1ccccc1)c1ccccc1 FGRBYDKOBBBPOI-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- OSBLTNPMIGYQGY-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;boric acid Chemical compound OB(O)O.OCC(N)(CO)CO.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O OSBLTNPMIGYQGY-UHFFFAOYSA-N 0.000 description 1
- UDOGNMDURIJYQC-UHFFFAOYSA-N 2-amino-6-methyl-1h-pteridin-4-one Chemical compound N1C(N)=NC(=O)C2=NC(C)=CN=C21 UDOGNMDURIJYQC-UHFFFAOYSA-N 0.000 description 1
- 239000005725 8-Hydroxyquinoline Substances 0.000 description 1
- 101150006240 AOX2 gene Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000009346 Adenosine receptors Human genes 0.000 description 1
- 108050000203 Adenosine receptors Proteins 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 102100036826 Aldehyde oxidase Human genes 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 238000010173 Alzheimer-disease mouse model Methods 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 108010006591 Apoenzymes Proteins 0.000 description 1
- 230000007082 Aβ accumulation Effects 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 238000009010 Bradford assay Methods 0.000 description 1
- 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 description 1
- 239000012619 Butyl Sepharose® Substances 0.000 description 1
- 239000012617 Butyl Sepharose™ 4 Fast Flow Substances 0.000 description 1
- 240000001432 Calendula officinalis Species 0.000 description 1
- 235000005881 Calendula officinalis Nutrition 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 108020004638 Circular DNA Proteins 0.000 description 1
- 101000749287 Clitocybe nebularis Clitocypin Proteins 0.000 description 1
- 101000767029 Clitocybe nebularis Clitocypin-1 Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 229940094664 Cysteine protease inhibitor Drugs 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 108091092584 GDNA Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101100175482 Glycine max CG-3 gene Proteins 0.000 description 1
- NMJREATYWWNIKX-UHFFFAOYSA-N GnRH Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CC(C)C)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 NMJREATYWWNIKX-UHFFFAOYSA-N 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000928314 Homo sapiens Aldehyde oxidase Proteins 0.000 description 1
- 101000585397 Homo sapiens Glutaminyl-peptide cyclotransferase-like protein Proteins 0.000 description 1
- 101000611951 Homo sapiens Platelet-derived growth factor subunit B Proteins 0.000 description 1
- 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 1
- YZJSUQQZGCHHNQ-UHFFFAOYSA-N Homoglutamine Chemical compound OC(=O)C(N)CCCC(N)=O YZJSUQQZGCHHNQ-UHFFFAOYSA-N 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010021929 Infertility male Diseases 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 208000027747 Kennedy disease Diseases 0.000 description 1
- ZQISRDCJNBUVMM-UHFFFAOYSA-N L-Histidinol Natural products OCC(N)CC1=CN=CN1 ZQISRDCJNBUVMM-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- ZQISRDCJNBUVMM-YFKPBYRVSA-N L-histidinol Chemical compound OC[C@@H](N)CC1=CNC=N1 ZQISRDCJNBUVMM-YFKPBYRVSA-N 0.000 description 1
- 239000006142 Luria-Bertani Agar Substances 0.000 description 1
- 208000007466 Male Infertility Diseases 0.000 description 1
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- 241000713869 Moloney murine leukemia virus Species 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- LRJUYAVTHIEHAI-LHBNDURVSA-N Muristerone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H]([C@H](O)C[C@@]3([C@@H]([C@@](C)(O)[C@H](O)CCC(C)C)CC[C@]33O)C)C3=CC(=O)[C@@]21O LRJUYAVTHIEHAI-LHBNDURVSA-N 0.000 description 1
- 102000005604 Myosin Heavy Chains Human genes 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- GHAZCVNUKKZTLG-UHFFFAOYSA-N N-ethyl-succinimide Natural products CCN1C(=O)CCC1=O GHAZCVNUKKZTLG-UHFFFAOYSA-N 0.000 description 1
- HDFGOPSGAURCEO-UHFFFAOYSA-N N-ethylmaleimide Chemical compound CCN1C(=O)C=CC1=O HDFGOPSGAURCEO-UHFFFAOYSA-N 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 102000008763 Neurofilament Proteins Human genes 0.000 description 1
- 108010088373 Neurofilament Proteins Proteins 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 238000010222 PCR analysis Methods 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 208000037658 Parkinson-dementia complex of Guam Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 1
- 108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 1
- 241000235648 Pichia Species 0.000 description 1
- 101710103494 Platelet-derived growth factor subunit B Proteins 0.000 description 1
- 102100040990 Platelet-derived growth factor subunit B Human genes 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 101150035356 Qpct gene Proteins 0.000 description 1
- 230000004570 RNA-binding Effects 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 238000011530 RNeasy Mini Kit Methods 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 1
- 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 241000710960 Sindbis virus Species 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 239000008051 TBE buffer Substances 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 241000589500 Thermus aquaticus Species 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 1
- 239000005862 Whey Substances 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 206010000210 abortion Diseases 0.000 description 1
- 231100000176 abortion Toxicity 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 230000030120 acrosome reaction Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000006933 amyloid-beta aggregation Effects 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical group N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
- 239000003693 atypical antipsychotic agent Substances 0.000 description 1
- 229940127236 atypical antipsychotics Drugs 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 102000023732 binding proteins Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000003491 cAMP production Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- KLOIYEQEVSIOOO-UHFFFAOYSA-N carbocromen Chemical compound CC1=C(CCN(CC)CC)C(=O)OC2=CC(OCC(=O)OCC)=CC=C21 KLOIYEQEVSIOOO-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000001925 catabolic effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000011437 continuous method Methods 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 230000002254 contraceptive effect Effects 0.000 description 1
- 210000003618 cortical neuron Anatomy 0.000 description 1
- GLNDAGDHSLMOKX-UHFFFAOYSA-N coumarin 120 Chemical compound C1=C(N)C=CC2=C1OC(=O)C=C2C GLNDAGDHSLMOKX-UHFFFAOYSA-N 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000012154 double-distilled water Substances 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000003890 endocrine cell Anatomy 0.000 description 1
- 230000002367 endolytic effect Effects 0.000 description 1
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000004720 fertilization Effects 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 238000007421 fluorometric assay Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 238000010363 gene targeting Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 210000001654 germ layer Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 230000009688 glial response Effects 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000005090 green fluorescent protein Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical group [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000003137 locomotive effect Effects 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000005044 neurofilament Anatomy 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000005257 nucleotidylation Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229960003540 oxyquinoline Drugs 0.000 description 1
- KLAKIAVEMQMVBT-UHFFFAOYSA-N p-hydroxy-phenacyl alcohol Natural products OCC(=O)C1=CC=C(O)C=C1 KLAKIAVEMQMVBT-UHFFFAOYSA-N 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000004963 pathophysiological condition Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000006919 peptide aggregation Effects 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 229940012982 picot Drugs 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000007026 protein scission Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 230000007420 reactivation Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 230000000698 schizophrenic effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000004739 secretory vesicle Anatomy 0.000 description 1
- 238000000822 sequential centrifugation Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- TUGDLVFMIQZYPA-UHFFFAOYSA-N tetracopper;tetrazinc Chemical compound [Cu+2].[Cu+2].[Cu+2].[Cu+2].[Zn+2].[Zn+2].[Zn+2].[Zn+2] TUGDLVFMIQZYPA-UHFFFAOYSA-N 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000563 toxic property Toxicity 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000003151 transfection method Methods 0.000 description 1
- 238000012301 transgenic model Methods 0.000 description 1
- 229910001428 transition metal ion Inorganic materials 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 210000004340 zona pellucida Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/1025—Acyltransferases (2.3)
- C12N9/104—Aminoacyltransferases (2.3.2)
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
- A01K2217/052—Animals comprising random inserted nucleic acids (transgenic) inducing gain of function
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
- A01K2267/0312—Animal model for Alzheimer's disease
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
- A01K2267/0318—Animal model for neurodegenerative disease, e.g. non- Alzheimer's
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Neurology (AREA)
- Immunology (AREA)
- Neurosurgery (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Environmental Sciences (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Diabetes (AREA)
- Physics & Mathematics (AREA)
- Biodiversity & Conservation Biology (AREA)
- Rheumatology (AREA)
- Animal Husbandry (AREA)
- Endocrinology (AREA)
- Biophysics (AREA)
- Hematology (AREA)
- Reproductive Health (AREA)
- Plant Pathology (AREA)
- Psychology (AREA)
- Urology & Nephrology (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US88564907P | 2007-01-19 | 2007-01-19 | |
| US885649P | 2007-01-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2372229T3 true ES2372229T3 (es) | 2012-01-17 |
Family
ID=39271322
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES08707977T Active ES2372229T3 (es) | 2007-01-19 | 2008-01-18 | Modelos de selección in vivo para el tratamiento de la enfermedad de alzheimer y otros trastornos relacionados con qpct. |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20080200567A1 (enExample) |
| EP (2) | EP2121944B1 (enExample) |
| JP (1) | JP2010516235A (enExample) |
| AT (1) | ATE521711T1 (enExample) |
| AU (1) | AU2008206936B2 (enExample) |
| CA (1) | CA2675192A1 (enExample) |
| DK (1) | DK2121944T3 (enExample) |
| ES (1) | ES2372229T3 (enExample) |
| HR (1) | HRP20110651T1 (enExample) |
| NZ (1) | NZ578513A (enExample) |
| SI (1) | SI2121944T1 (enExample) |
| WO (1) | WO2008087197A1 (enExample) |
| ZA (1) | ZA200904353B (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9277737B2 (en) | 2006-09-21 | 2016-03-08 | Probiodrug Ag | Mouse models carrying a knock-out mutation of the QPCTL-gene |
| JP5612860B2 (ja) * | 2007-03-09 | 2014-10-22 | プロビオドルグ エージー | グルタミニルシクラーゼ阻害剤としてのイミダゾ［１，５−ａ］ピリジン誘導体 |
| JP5675341B2 (ja) * | 2007-04-18 | 2015-02-25 | プロビオドルグ エージー | グルタミニルシクラーゼ阻害剤としてのチオキソキナゾリノン誘導体 |
| ES2473621T3 (es) * | 2007-04-18 | 2014-07-07 | Probiodrug Ag | Derivados de nitrovinil-diamina como inhibidores de glutaminil ciclasa |
| WO2008128986A1 (en) * | 2007-04-18 | 2008-10-30 | Probiodrug Ag | Urea derivatives as glutaminyl cyclase inhibitors |
| JP5675340B2 (ja) * | 2007-04-18 | 2015-02-25 | プロビオドルグ エージー | 新規阻害剤 |
| WO2008128983A1 (en) * | 2007-04-18 | 2008-10-30 | Probiodrug Ag | Cyano-guanidine derivatives as glutaminyl cyclase inhibitors |
| DK2142514T3 (da) * | 2007-04-18 | 2015-03-23 | Probiodrug Ag | Thioureaderivater som glutaminylcyclase-inhibitorer |
| WO2008128984A1 (en) * | 2007-04-20 | 2008-10-30 | Probiodrug Ag | Aminopyrimidine derivatives as glutaminyl cyclase inhibitors |
| NZ583799A (en) * | 2007-09-12 | 2011-12-22 | Probiodrug Ag | Transgenic mice comprising a DNA transgene encoding ABeta peptide |
| WO2009090190A1 (en) * | 2008-01-14 | 2009-07-23 | Probiodrug Ag | Mouse models carrying a knock-out mutation of the glutaminyl cyclase gene |
| EA025107B1 (ru) * | 2008-07-31 | 2016-11-30 | Пробиодруг Аг | Способ диагностирования болезни альцгеймера, нейродегенерации при синдроме дауна или легкого когнитивного нарушения у субъекта (варианты) и набор для осуществления способа |
| US11219696B2 (en) * | 2008-12-19 | 2022-01-11 | Nationwide Children's Hospital | Delivery of polynucleotides using recombinant AAV9 |
| ES2540467T3 (es) | 2010-08-19 | 2015-07-09 | Probiodrug Ag | Estructura cristalina de glutaminil ciclasa |
| JP2013541938A (ja) | 2010-09-02 | 2013-11-21 | プロビオドルグ エージー | アイソｑｃ関連障害の治療のためのインビボスクリーニングモデル |
| EP2635675B1 (en) | 2010-11-02 | 2016-01-06 | Probiodrug AG | Crystal structure of isoglutaminyl cyclase |
| US20130052203A1 (en) | 2011-08-12 | 2013-02-28 | Probiodrug Ag | In vivo screening models for treatment of qc-related disorders |
| BR112015002168A2 (pt) | 2012-08-01 | 2017-11-07 | Nationwide Childrens Hospital | liberação intratecal de vírus 9 adeno-associado recombinante |
| US20180318260A1 (en) * | 2015-11-04 | 2018-11-08 | The Scripps Research Institute | Compositions and methods for treating cystic fibrosis |
| MC200185B1 (fr) | 2016-09-16 | 2017-10-04 | Coronal Audio | Dispositif et procédé de captation et traitement d'un champ acoustique tridimensionnel |
| MC200186B1 (fr) | 2016-09-30 | 2017-10-18 | Coronal Encoding | Procédé de conversion, d'encodage stéréophonique, de décodage et de transcodage d'un signal audio tridimensionnel |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4873191A (en) | 1981-06-12 | 1989-10-10 | Ohio University | Genetic transformation of zygotes |
| DE122007000007I2 (de) | 1986-04-09 | 2010-12-30 | Genzyme Corp | Genetisch transformierte Tiere, die ein gewünschtes Protein in Milch absondern |
| US4873316A (en) | 1987-06-23 | 1989-10-10 | Biogen, Inc. | Isolation of exogenous recombinant proteins from the milk of transgenic mammals |
| US5175384A (en) | 1988-12-05 | 1992-12-29 | Genpharm International | Transgenic mice depleted in mature t-cells and methods for making transgenic mice |
| GB8901778D0 (en) | 1989-01-27 | 1989-03-15 | Univ Court Of The University O | Manipulatory technique |
| US5602299A (en) | 1992-09-23 | 1997-02-11 | Mount Sinai School Of Medicine Of The City University Of New York | Transgenic animal models for neurodegenerative disease |
| JPH07132033A (ja) | 1993-11-12 | 1995-05-23 | Hoechst Japan Ltd | アルツハイマー病モデルトランスジェニック動物 |
| US6066778A (en) | 1996-11-06 | 2000-05-23 | The Regents Of The University Of Michigan | Transgenic mice expressing APC resistant factor V |
| US5981830A (en) | 1997-05-30 | 1999-11-09 | Schering Aktiengesellschaft | Knockout mice and their progeny with a disrupted hepsin gene |
| US6948038B2 (en) * | 2001-07-24 | 2005-09-20 | Microsoft Corporation | System and method for backing up and restoring data |
| PL1620082T3 (pl) | 2003-05-05 | 2010-10-29 | Probiodrug Ag | Medyczne zastosowanie inhibitorów cyklazy glutaminylowej i glutaminianowej do leczenia choroby Alzheimera i zespołu Downa |
| DE602004026289D1 (de) * | 2003-05-05 | 2010-05-12 | Probiodrug Ag | Glutaminylcyclase-hemmer |
| DK2206496T3 (da) * | 2003-05-05 | 2014-12-15 | Probiodrug Ag | Screening af inhibitorer af pyroglutaminsyredannelse i amyloid beta-peptid |
| AU2004290499C1 (en) * | 2003-11-03 | 2011-02-24 | Probiodrug Ag | Combinations useful for the treatment of neuronal disorders |
| AU2005210004B2 (en) * | 2004-02-05 | 2010-10-28 | Probiodrug Ag | Novel inhibitors of glutaminyl cyclase |
| GB0704100D0 (en) | 2006-03-17 | 2007-04-11 | Vodafone Plc | Improvements in an ehspa architecture |
| MX2009003090A (es) * | 2006-09-21 | 2009-04-02 | Probiodrug Ag | Genes novedosos relacionados con ciclasa de glutaminilo. |
-
2008
- 2008-01-18 AU AU2008206936A patent/AU2008206936B2/en not_active Ceased
- 2008-01-18 EP EP08707977A patent/EP2121944B1/en not_active Not-in-force
- 2008-01-18 NZ NZ578513A patent/NZ578513A/en not_active IP Right Cessation
- 2008-01-18 AT AT08707977T patent/ATE521711T1/de active
- 2008-01-18 ZA ZA200904353A patent/ZA200904353B/xx unknown
- 2008-01-18 ES ES08707977T patent/ES2372229T3/es active Active
- 2008-01-18 WO PCT/EP2008/050532 patent/WO2008087197A1/en not_active Ceased
- 2008-01-18 EP EP11178419A patent/EP2395095A1/en not_active Withdrawn
- 2008-01-18 HR HR20110651T patent/HRP20110651T1/hr unknown
- 2008-01-18 CA CA002675192A patent/CA2675192A1/en not_active Abandoned
- 2008-01-18 US US12/016,266 patent/US20080200567A1/en not_active Abandoned
- 2008-01-18 SI SI200830434T patent/SI2121944T1/sl unknown
- 2008-01-18 DK DK08707977.8T patent/DK2121944T3/da active
- 2008-01-18 JP JP2009545932A patent/JP2010516235A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| DK2121944T3 (da) | 2011-10-31 |
| CA2675192A1 (en) | 2008-07-24 |
| ZA200904353B (en) | 2010-09-29 |
| EP2121944B1 (en) | 2011-08-24 |
| AU2008206936A1 (en) | 2008-07-24 |
| SI2121944T1 (sl) | 2011-12-30 |
| HRP20110651T1 (hr) | 2011-10-31 |
| WO2008087197A1 (en) | 2008-07-24 |
| JP2010516235A (ja) | 2010-05-20 |
| NZ578513A (en) | 2012-01-12 |
| AU2008206936B2 (en) | 2013-03-14 |
| EP2121944A1 (en) | 2009-11-25 |
| US20080200567A1 (en) | 2008-08-21 |
| EP2395095A1 (en) | 2011-12-14 |
| ATE521711T1 (de) | 2011-09-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2372229T3 (es) | Modelos de selección in vivo para el tratamiento de la enfermedad de alzheimer y otros trastornos relacionados con qpct. | |
| US8283517B2 (en) | Transgenic mouse models of Aβ overexpression | |
| EP2432314B1 (en) | Mouse models carrying a knock-out mutation of the qpctl-gene | |
| EP2238252B1 (en) | Mouse models carrying a knock-out mutation of the glutaminyl cyclase gene | |
| US20130052203A1 (en) | In vivo screening models for treatment of qc-related disorders | |
| Stephan5Halle et al. | Demuth et al.(43) Pub. Date: Oct. 31, 2013 | |
| US9277737B2 (en) | Mouse models carrying a knock-out mutation of the QPCTL-gene | |
| TOWER | Schilling et al.(43) Pub. Date: Jul. 16, 2009 | |
| WO2012028706A1 (en) | IN VIVO SCREENING MODELS FOR TREATMENT OF isoQC-RELATED DISORDERS | |
| WO2004062627A9 (en) | In vivo screening models for treatment of alzheimer's disease and other neurodegenerative disorders | |
| Bader et al. | Transgenic Animal Models In | |
| US20030024000A1 (en) | Radical fringe proteins modulate wound healing and keratinocyte proliferation | |
| HK1146735A (en) | Transgenic mice |