ES2412268T3 - Alteraciones específicas de la Enfermedad de Alzheimer de la relación de fosforilación ERK1/ERK2 como biomarcadores moleculares específicos de la Enfermedad de Alzheimer (ADSMB) - Google Patents
Alteraciones específicas de la Enfermedad de Alzheimer de la relación de fosforilación ERK1/ERK2 como biomarcadores moleculares específicos de la Enfermedad de Alzheimer (ADSMB) Download PDFInfo
- Publication number
- ES2412268T3 ES2412268T3 ES08020258T ES08020258T ES2412268T3 ES 2412268 T3 ES2412268 T3 ES 2412268T3 ES 08020258 T ES08020258 T ES 08020258T ES 08020258 T ES08020258 T ES 08020258T ES 2412268 T3 ES2412268 T3 ES 2412268T3
- Authority
- ES
- Spain
- Prior art keywords
- disease
- alzheimer
- cells
- erk1
- specific molecular
- 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
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 198
- 239000000090 biomarker Substances 0.000 title claims abstract description 66
- 230000026731 phosphorylation Effects 0.000 title description 32
- 238000006366 phosphorylation reaction Methods 0.000 title description 32
- 230000004075 alteration Effects 0.000 title description 4
- 101000876610 Dictyostelium discoideum Extracellular signal-regulated kinase 2 Proteins 0.000 title description 2
- 101001052493 Homo sapiens Mitogen-activated protein kinase 1 Proteins 0.000 title description 2
- 108040008097 MAP kinase activity proteins Proteins 0.000 title description 2
- 102000019149 MAP kinase activity proteins Human genes 0.000 title description 2
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 title description 2
- 101150018665 MAPK3 gene Proteins 0.000 claims abstract description 58
- 150000001875 compounds Chemical class 0.000 claims abstract description 51
- 102000003923 Protein Kinase C Human genes 0.000 claims abstract description 50
- 108090000315 Protein Kinase C Proteins 0.000 claims abstract description 50
- 238000000034 method Methods 0.000 claims abstract description 49
- 101150024075 Mapk1 gene Proteins 0.000 claims abstract description 34
- 239000012190 activator Substances 0.000 claims abstract description 34
- 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 claims abstract description 33
- 238000012360 testing method Methods 0.000 claims abstract description 23
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 8
- 210000004027 cell Anatomy 0.000 claims description 163
- 101800004538 Bradykinin Proteins 0.000 claims description 58
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 claims description 58
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 claims description 57
- 210000002950 fibroblast Anatomy 0.000 claims description 43
- 210000000321 buccal mucosa cell Anatomy 0.000 claims description 6
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 6
- 210000004927 skin cell Anatomy 0.000 claims description 5
- 229940056854 bio-statin Drugs 0.000 claims description 4
- -1 biostatin Chemical compound 0.000 claims description 4
- 210000004369 blood Anatomy 0.000 claims description 4
- 239000008280 blood Substances 0.000 claims description 4
- PXGPLTODNUVGFL-BRIYLRKRSA-N (E,Z)-(1R,2R,3R,5S)-7-(3,5-Dihydroxy-2-((3S)-(3-hydroxy-1-octenyl))cyclopentyl)-5-heptenoic acid Chemical compound CCCCC[C@H](O)C=C[C@H]1[C@H](O)C[C@H](O)[C@@H]1CC=CCCCC(O)=O PXGPLTODNUVGFL-BRIYLRKRSA-N 0.000 claims description 3
- 108010051479 Bombesin Proteins 0.000 claims description 3
- 102000013585 Bombesin Human genes 0.000 claims description 3
- 101800001982 Cholecystokinin Proteins 0.000 claims description 3
- 102100025841 Cholecystokinin Human genes 0.000 claims description 3
- 108090000190 Thrombin Proteins 0.000 claims description 3
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 claims description 3
- 108010004977 Vasopressins Proteins 0.000 claims description 3
- 102000002852 Vasopressins Human genes 0.000 claims description 3
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 claims description 3
- DNDCVAGJPBKION-DOPDSADYSA-N bombesin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1NC2=CC=CC=C2C=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1NC(=O)CC1)C(C)C)C1=CN=CN1 DNDCVAGJPBKION-DOPDSADYSA-N 0.000 claims description 3
- 229940107137 cholecystokinin Drugs 0.000 claims description 3
- 210000003296 saliva Anatomy 0.000 claims description 3
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 claims description 3
- 229960004072 thrombin Drugs 0.000 claims description 3
- 210000002700 urine Anatomy 0.000 claims description 3
- 229960003726 vasopressin Drugs 0.000 claims description 3
- 208000012299 Alzheimer disease 5 Diseases 0.000 claims 1
- 102100035792 Kininogen-1 Human genes 0.000 claims 1
- PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 claims 1
- 102400000967 Bradykinin Human genes 0.000 description 57
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
- 108090000623 proteins and genes Proteins 0.000 description 30
- 102000004169 proteins and genes Human genes 0.000 description 28
- 102000043136 MAP kinase family Human genes 0.000 description 27
- 108091054455 MAP kinase family Proteins 0.000 description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 26
- 201000010099 disease Diseases 0.000 description 25
- 206010012289 Dementia Diseases 0.000 description 22
- 108090000765 processed proteins & peptides Proteins 0.000 description 22
- 230000035945 sensitivity Effects 0.000 description 21
- 238000003556 assay Methods 0.000 description 20
- 238000002405 diagnostic procedure Methods 0.000 description 20
- 239000002609 medium Substances 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 210000001519 tissue Anatomy 0.000 description 16
- 210000001626 skin fibroblast Anatomy 0.000 description 15
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 13
- 238000012216 screening Methods 0.000 description 13
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 12
- 235000011089 carbon dioxide Nutrition 0.000 description 12
- 210000002966 serum Anatomy 0.000 description 12
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 12
- 238000011888 autopsy Methods 0.000 description 11
- 102000004196 processed proteins & peptides Human genes 0.000 description 11
- 238000001262 western blot Methods 0.000 description 11
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 10
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 10
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 10
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 9
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 9
- 208000023105 Huntington disease Diseases 0.000 description 9
- 208000018737 Parkinson disease Diseases 0.000 description 9
- 238000003745 diagnosis Methods 0.000 description 9
- 238000005259 measurement Methods 0.000 description 9
- 230000002093 peripheral effect Effects 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000003018 immunoassay Methods 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000012546 transfer Methods 0.000 description 8
- 230000005856 abnormality Effects 0.000 description 7
- 150000001413 amino acids Chemical group 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 238000012790 confirmation Methods 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 229930182555 Penicillin Natural products 0.000 description 6
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000004113 cell culture Methods 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 230000003834 intracellular effect Effects 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 229940049954 penicillin Drugs 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- 229960005322 streptomycin Drugs 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 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 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 239000013592 cell lysate Substances 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 5
- 210000002569 neuron Anatomy 0.000 description 5
- 239000012679 serum free medium Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 102000013498 tau Proteins Human genes 0.000 description 5
- 108010026424 tau Proteins Proteins 0.000 description 5
- 102000001267 GSK3 Human genes 0.000 description 4
- 239000000020 Nitrocellulose Substances 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- 229920004890 Triton X-100 Polymers 0.000 description 4
- 239000013504 Triton X-100 Substances 0.000 description 4
- 102000014384 Type C Phospholipases Human genes 0.000 description 4
- 108010079194 Type C Phospholipases Proteins 0.000 description 4
- 238000001574 biopsy Methods 0.000 description 4
- 210000000601 blood cell Anatomy 0.000 description 4
- 230000005754 cellular signaling Effects 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 238000012417 linear regression Methods 0.000 description 4
- 239000012139 lysis buffer Substances 0.000 description 4
- 229920001220 nitrocellulos Polymers 0.000 description 4
- 238000010606 normalization Methods 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 201000000980 schizophrenia Diseases 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000011550 stock solution Substances 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- 238000002604 ultrasonography Methods 0.000 description 4
- 101710085045 B2 bradykinin receptor Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-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
- 229940122907 Phosphatase inhibitor Drugs 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000013399 early diagnosis Methods 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000002731 protein assay Methods 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000013049 sediment Substances 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 238000007390 skin biopsy Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 239000011534 wash buffer Substances 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 2
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 2
- 108050001736 Bradykinin receptor Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- MMWCIQZXVOZEGG-XJTPDSDZSA-N D-myo-Inositol 1,4,5-trisphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H](O)[C@@H]1OP(O)(O)=O MMWCIQZXVOZEGG-XJTPDSDZSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 108010044467 Isoenzymes Proteins 0.000 description 2
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 206010029350 Neurotoxicity Diseases 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 101100463797 Rattus norvegicus Pgrmc1 gene Proteins 0.000 description 2
- 239000012722 SDS sample buffer Substances 0.000 description 2
- 206010044221 Toxic encephalopathy Diseases 0.000 description 2
- 229940076850 Tyrosine phosphatase inhibitor Drugs 0.000 description 2
- SXEHKFHPFVVDIR-UHFFFAOYSA-N [4-(4-hydrazinylphenyl)phenyl]hydrazine Chemical compound C1=CC(NN)=CC=C1C1=CC=C(NN)C=C1 SXEHKFHPFVVDIR-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000003759 clinical diagnosis Methods 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000011539 homogenization buffer Substances 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 238000001114 immunoprecipitation Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000009593 lumbar puncture Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 230000007135 neurotoxicity Effects 0.000 description 2
- 231100000228 neurotoxicity Toxicity 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000007310 pathophysiology Effects 0.000 description 2
- 108010091748 peptide A Proteins 0.000 description 2
- 150000003905 phosphatidylinositols Chemical class 0.000 description 2
- 108091005981 phosphorylated proteins Proteins 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- LUZOFMGZMUZSSK-LRDDRELGSA-N (-)-indolactam V Chemical compound C1[C@@H](CO)NC(=O)[C@H](C(C)C)N(C)C2=CC=CC3=C2C1=CN3 LUZOFMGZMUZSSK-LRDDRELGSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- ZQBULZYTDGUSSK-KRWDZBQOSA-N 1,2-dioctanoyl-sn-glycerol Chemical compound CCCCCCCC(=O)OC[C@H](CO)OC(=O)CCCCCCC ZQBULZYTDGUSSK-KRWDZBQOSA-N 0.000 description 1
- PWTCCMJTPHCGMS-YRBAHSOBSA-N 1-Oleoyl-2-acetyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](CO)OC(C)=O PWTCCMJTPHCGMS-YRBAHSOBSA-N 0.000 description 1
- RYCNUMLMNKHWPZ-SNVBAGLBSA-N 1-acetyl-sn-glycero-3-phosphocholine Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C RYCNUMLMNKHWPZ-SNVBAGLBSA-N 0.000 description 1
- NSXLMTYRMFVYNT-IUJDHQGTSA-N 1-stearoyl-2-arachidonoyl-sn-glycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](CO)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC NSXLMTYRMFVYNT-IUJDHQGTSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QMGUOJYZJKLOLH-UHFFFAOYSA-N 3-[1-[3-(dimethylamino)propyl]indol-3-yl]-4-(1h-indol-3-yl)pyrrole-2,5-dione Chemical compound C12=CC=CC=C2N(CCCN(C)C)C=C1C1=C(C=2C3=CC=CC=C3NC=2)C(=O)NC1=O QMGUOJYZJKLOLH-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 1
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 1
- 102000004149 Annexin A2 Human genes 0.000 description 1
- 108090000668 Annexin A2 Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102000010183 Bradykinin receptor Human genes 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 206010008096 Cerebral atrophy Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 102000005636 Cyclic AMP Response Element-Binding Protein Human genes 0.000 description 1
- 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- 238000009007 Diagnostic Kit Methods 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 108060006662 GSK3 Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- JKVOKRQJEYPKQG-UHFFFAOYSA-N Gnidimacrin Natural products CC1CCCCCCC(O)C23OC4C5C6OC6(CO)C(O)C7(O)C(OC(=O)c8ccccc8)C(C)C1C7C5(O2)C(CC4(O3)C(=C)C)OC(=O)c9ccccc9 JKVOKRQJEYPKQG-UHFFFAOYSA-N 0.000 description 1
- LUZOFMGZMUZSSK-UHFFFAOYSA-N Indolactam-V Natural products C1C(CO)NC(=O)C(C(C)C)N(C)C2=CC=CC3=C2C1=CN3 LUZOFMGZMUZSSK-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 125000000769 L-threonyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])[C@](O[H])(C([H])([H])[H])[H] 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 241000187723 Micromonospora sp. Species 0.000 description 1
- 102000044589 Mitogen-Activated Protein Kinase 1 Human genes 0.000 description 1
- 102000046795 Mitogen-Activated Protein Kinase 3 Human genes 0.000 description 1
- 108700027649 Mitogen-Activated Protein Kinase 3 Proteins 0.000 description 1
- 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 1
- 244000111261 Mucuna pruriens Species 0.000 description 1
- 235000006161 Mucuna pruriens Nutrition 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 241001263604 Stellera chamaejasme Species 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 235000018936 Vitellaria paradoxa Nutrition 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000003942 amyloidogenic effect Effects 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000008238 biochemical pathway Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 230000004094 calcium homeostasis Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 150000001841 cholesterols Chemical class 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000002967 competitive immunoassay Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 229940095074 cyclic amp Drugs 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 230000030609 dephosphorylation Effects 0.000 description 1
- 238000006209 dephosphorylation reaction Methods 0.000 description 1
- 150000001982 diacylglycerols Chemical class 0.000 description 1
- VIGVRXYWWFPORY-UHFFFAOYSA-N diphenylborinic acid Chemical compound C=1C=CC=CC=1B(O)C1=CC=CC=C1 VIGVRXYWWFPORY-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000011536 extraction buffer Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- SSXCVTWCXHGTLK-VFZTWJSWSA-N gnidimacrin Chemical compound O([C@H]1[C@H]([C@H]2[C@@H]3[C@]1(O)[C@@H]([C@@]1(CO)O[C@H]1[C@H]1[C@H]4O[C@]5(O[C@@]31[C@H](COC(=O)C=1C=CC=CC=1)C[C@@]4(O5)C(C)=C)[C@H](O)CCCCCC[C@H]2C)O)C)C(=O)C1=CC=CC=C1 SSXCVTWCXHGTLK-VFZTWJSWSA-N 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 238000000760 immunoelectrophoresis Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000037456 inflammatory mechanism Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- IXAQOQZEOGMIQS-SSQFXEBMSA-M lipoxin A4(1-) Chemical compound CCCCC[C@H](O)\C=C\C=C/C=C/C=C/[C@@H](O)[C@@H](O)CCCC([O-])=O IXAQOQZEOGMIQS-SSQFXEBMSA-M 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 150000007931 macrolactones Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 238000002324 minimally invasive surgery Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- NFVJNJQRWPQVOA-UHFFFAOYSA-N n-[2-chloro-5-(trifluoromethyl)phenyl]-2-[3-(4-ethyl-5-ethylsulfanyl-1,2,4-triazol-3-yl)piperidin-1-yl]acetamide Chemical compound CCN1C(SCC)=NN=C1C1CN(CC(=O)NC=2C(=CC=C(C=2)C(F)(F)F)Cl)CCC1 NFVJNJQRWPQVOA-UHFFFAOYSA-N 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000004963 pathophysiological condition Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 150000004633 phorbol derivatives Chemical class 0.000 description 1
- 239000002644 phorbol ester Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000002331 protein detection Methods 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000009822 protein phosphorylation Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000007388 punch biopsy Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000012089 stop solution Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- UUUGYDOQQLOJQA-UHFFFAOYSA-L vanadyl sulfate Chemical compound [V+2]=O.[O-]S([O-])(=O)=O UUUGYDOQQLOJQA-UHFFFAOYSA-L 0.000 description 1
- 229940041260 vanadyl sulfate Drugs 0.000 description 1
- 229910000352 vanadyl sulfate Inorganic materials 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5091—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing the pathological state of an organism
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
- G01N2333/4701—Details
- G01N2333/4709—Amyloid plaque core protein
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/91—Transferases (2.)
- G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/28—Neurological disorders
- G01N2800/2814—Dementia; Cognitive disorders
- G01N2800/2821—Alzheimer
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Pathology (AREA)
- Microbiology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physiology (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Pharmacology & Pharmacy (AREA)
- Psychiatry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| WOPCT/US2005/036014 | 2005-10-11 | ||
| PCT/US2005/036014 WO2007043998A1 (en) | 2005-10-11 | 2005-10-11 | Alzheimer’s disease-specific alterations of the erk1/erk2 phosphorylation ratio |
| US11/246,524 US7595167B2 (en) | 2005-10-11 | 2005-10-11 | Alzheimer's disease-specific alterations of the Erk1/Erk2 phosphorylation ratio |
| US246524 | 2005-10-11 | ||
| WOPCT/US2006/022156 | 2006-06-07 | ||
| PCT/US2006/022156 WO2007044094A1 (en) | 2005-10-11 | 2006-06-07 | Alzheimer's disease-specific alterations of the erk1/erk2 phosphorylation ratio as alzheimer's disease-specific molecular biomarkers (adsmb) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2412268T3 true ES2412268T3 (es) | 2013-07-10 |
Family
ID=37067652
Family Applications (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES08020258T Active ES2412268T3 (es) | 2005-10-11 | 2006-09-25 | Alteraciones específicas de la Enfermedad de Alzheimer de la relación de fosforilación ERK1/ERK2 como biomarcadores moleculares específicos de la Enfermedad de Alzheimer (ADSMB) |
| ES10011289.5T Active ES2596881T3 (es) | 2005-10-11 | 2006-09-25 | Kit para el diagnóstico de la Enfermedad de Alzheimer |
| ES10012836.2T Active ES2477284T3 (es) | 2005-10-11 | 2006-09-25 | Método de monitorización de la progresión de la enfermedad de Alzheimer por medición de un biomarcador |
| ES10011288.7T Active ES2588376T3 (es) | 2005-10-11 | 2006-09-25 | Procedimientos para la identificación de tratamientos de la enfermedad de Alzheimer |
| ES06825096T Active ES2323813T3 (es) | 2005-10-11 | 2006-09-25 | Alteraciones especificas de la enfermedad de alzheimer de la proporcion de fosforilacion erk1/erk2 - biomarcadores moleculares especificos de la enfermedad de alzheimer (adsmb). |
Family Applications After (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10011289.5T Active ES2596881T3 (es) | 2005-10-11 | 2006-09-25 | Kit para el diagnóstico de la Enfermedad de Alzheimer |
| ES10012836.2T Active ES2477284T3 (es) | 2005-10-11 | 2006-09-25 | Método de monitorización de la progresión de la enfermedad de Alzheimer por medición de un biomarcador |
| ES10011288.7T Active ES2588376T3 (es) | 2005-10-11 | 2006-09-25 | Procedimientos para la identificación de tratamientos de la enfermedad de Alzheimer |
| ES06825096T Active ES2323813T3 (es) | 2005-10-11 | 2006-09-25 | Alteraciones especificas de la enfermedad de alzheimer de la proporcion de fosforilacion erk1/erk2 - biomarcadores moleculares especificos de la enfermedad de alzheimer (adsmb). |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20180024146A1 (https=) |
| EP (5) | EP2322936A1 (https=) |
| JP (1) | JP4908514B2 (https=) |
| KR (2) | KR20140002073A (https=) |
| AT (1) | ATE431558T1 (https=) |
| CA (1) | CA2625300C (https=) |
| DE (1) | DE602006006855D1 (https=) |
| ES (5) | ES2412268T3 (https=) |
| TW (2) | TW201413246A (https=) |
| WO (1) | WO2007044094A1 (https=) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1549721B (zh) | 2001-02-27 | 2012-03-07 | 布朗歇特洛克菲勒神经科学研究所 | 基于促分裂原活化的蛋白激酶的磷酸化诊断阿尔茨海默氏病 |
| US20050065205A1 (en) | 2002-03-07 | 2005-03-24 | Daniel Alkon | Methods for Alzheimer's disease treatment and cognitive enhance |
| US6825229B2 (en) | 2002-03-07 | 2004-11-30 | Blanchette Rockefeller Neurosciences Institute | Methods for Alzheimer's Disease treatment and cognitive enhancement |
| TW201206425A (en) | 2004-05-18 | 2012-02-16 | Brni Neurosciences Inst | Treatment of depressive disorders |
| US7595167B2 (en) | 2005-10-11 | 2009-09-29 | Blanchette Rockefeller Neurosciences Institute | Alzheimer's disease-specific alterations of the Erk1/Erk2 phosphorylation ratio |
| US20090029873A1 (en) | 2005-10-11 | 2009-01-29 | Blanchette Rockefeller Neurosciences Institute | Alzheimer's Disease-Specific Alterations of the Erk1/Erk2 Phosphorylation Ratio-Alzheimer's Disease-Specific Molecular Biomarkers (Adsmb) |
| CN103961347A (zh) * | 2006-07-28 | 2014-08-06 | 布朗歇特洛克菲勒神经科学研究所 | 刺激细胞生长、突触重塑和巩固长期记忆的方法 |
| EP3332797A3 (en) | 2007-02-09 | 2018-08-01 | Blanchette Rockefeller Neurosciences Institute | Therapeutic effects of bryostatins, bryologs and other related substances on head trauma-induced memory impairment and brain injury |
| EP2669386A1 (en) | 2008-07-28 | 2013-12-04 | Blanchette Rockefeller Neurosciences Institute | Stimulus-elicited genomic profile markers of alzheimer's disease |
| WO2010014585A1 (en) | 2008-07-28 | 2010-02-04 | Blanchette Rockefeller Neurosciences Institute | Pkc-activating compounds for the treatment of neurodegenerative diseases |
| BRPI0914859A2 (pt) * | 2008-08-27 | 2015-11-03 | Lundbeck & Co As H | método para diagnosticar um distúrbio afetivo, produto de programa de computador, computador, e, método para determinar uma probabilidade de que um indivíduo de teste exiba um sintoma de um distúrbio afetivo |
| US8658134B2 (en) | 2009-10-02 | 2014-02-25 | Blanchette Rockefeller Neurosciences Institute | Fibroblast growth patterns for diagnosis of Alzheimer's disease |
| JP6013184B2 (ja) * | 2009-10-02 | 2016-10-25 | ブランシェット・ロックフェラー・ニューロサイエンスィズ・インスティテュート | アルツハイマー病末梢細胞におけるｐｋｃアイソザイムプロセッシングの異常変化 |
| CA2835686C (en) * | 2011-05-12 | 2019-10-01 | Florin V. Chirila | Peripheral diagnostic methods for screening alzheimer's disease using beta amyloid and intercellular communication |
| EP2780316B1 (en) | 2011-11-13 | 2020-04-15 | Blanchette Rockefeller Neurosciences Institute | Esters of dcpla and methods of treatment using the same |
| KR101351978B1 (ko) * | 2012-10-30 | 2014-01-16 | 주식회사 코씨드바이오팜 | 참치 안구 파쇄물을 유효성분으로 포함하는 관절염 예방 또는 치료용 약제학적 조성물 및 식품 조성물 |
| CA2935266C (en) * | 2014-01-03 | 2022-02-01 | Blanchette Rockefeller Neurosciences Institute | Convergence of aggregation rate with validated peripheral diagnostics for alzheimer's disease |
| US11415574B2 (en) | 2017-03-31 | 2022-08-16 | NeuroDiagnostics LLC | Lymphocyte-based morphometric test for alzheimer's disease |
| WO2020237203A1 (en) * | 2019-05-23 | 2020-11-26 | Indiana University Research And Technology Corporation | Methods for objective assessment of memory, early detection of risk for alzheimer's disease, matching individuals with treatments, monitoring response to treatment, and new methods of use for drugs |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4374316B2 (ja) * | 1993-01-25 | 2009-12-02 | 武田薬品工業株式会社 | β−アミロイドまたはその誘導体に対する抗体およびその用途 |
| US6107050A (en) | 1993-05-03 | 2000-08-22 | The United States Of America As Represented By The Department Of Health And Human Services | Diagnostic test for alzheimers disease |
| US20030108956A1 (en) * | 1993-05-03 | 2003-06-12 | Alkon Daniel L. | Cell tests for Alzheimer's disease |
| US7427392B1 (en) * | 1994-11-14 | 2008-09-23 | Elan Pharmaceuticals, Inc. | Methods for aiding in the diagnosis of alzheimer's disease by measuring amyloid-β peptide (x-≧41) and tau |
| US20030165481A1 (en) * | 2000-02-24 | 2003-09-04 | Hersh Louis B. | Amyloid peptide inactivating enzyme to treat Alzheimer's disease |
| CN1549721B (zh) * | 2001-02-27 | 2012-03-07 | 布朗歇特洛克菲勒神经科学研究所 | 基于促分裂原活化的蛋白激酶的磷酸化诊断阿尔茨海默氏病 |
| US6825229B2 (en) * | 2002-03-07 | 2004-11-30 | Blanchette Rockefeller Neurosciences Institute | Methods for Alzheimer's Disease treatment and cognitive enhancement |
| KR100574017B1 (ko) | 2003-08-11 | 2006-04-26 | 삼성전자주식회사 | 잉크젯 프린터의 잉크 카트리지 |
| US7199386B2 (en) | 2004-07-29 | 2007-04-03 | General Electric Company | System and method for detecting defects in a light-management film |
-
2006
- 2006-06-07 WO PCT/US2006/022156 patent/WO2007044094A1/en not_active Ceased
- 2006-09-25 KR KR1020137031223A patent/KR20140002073A/ko not_active Withdrawn
- 2006-09-25 DE DE602006006855T patent/DE602006006855D1/de active Active
- 2006-09-25 JP JP2008535546A patent/JP4908514B2/ja not_active Expired - Fee Related
- 2006-09-25 EP EP10011290A patent/EP2322936A1/en not_active Withdrawn
- 2006-09-25 CA CA2625300A patent/CA2625300C/en active Active
- 2006-09-25 ES ES08020258T patent/ES2412268T3/es active Active
- 2006-09-25 ES ES10011289.5T patent/ES2596881T3/es active Active
- 2006-09-25 EP EP10011288.7A patent/EP2339349B1/en active Active
- 2006-09-25 EP EP10011289.5A patent/EP2322934B1/en active Active
- 2006-09-25 EP EP10012836.2A patent/EP2317321B1/en active Active
- 2006-09-25 ES ES10012836.2T patent/ES2477284T3/es active Active
- 2006-09-25 ES ES10011288.7T patent/ES2588376T3/es active Active
- 2006-09-25 AT AT06825096T patent/ATE431558T1/de not_active IP Right Cessation
- 2006-09-25 EP EP08020258A patent/EP2031398B1/en active Active
- 2006-09-25 ES ES06825096T patent/ES2323813T3/es active Active
- 2006-10-11 TW TW102146766A patent/TW201413246A/zh unknown
- 2006-10-11 TW TW095137389A patent/TWI448688B/zh not_active IP Right Cessation
-
2008
- 2008-05-08 KR KR1020087011105A patent/KR101375552B1/ko not_active Expired - Fee Related
-
2017
- 2017-09-29 US US15/719,714 patent/US20180024146A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| TWI448688B (zh) | 2014-08-11 |
| EP2322934A1 (en) | 2011-05-18 |
| EP2031398B1 (en) | 2013-02-13 |
| CA2625300A1 (en) | 2007-04-26 |
| EP2317321B1 (en) | 2014-04-02 |
| ES2596881T3 (es) | 2017-01-12 |
| EP2322934B1 (en) | 2016-08-31 |
| KR20140002073A (ko) | 2014-01-07 |
| ES2323813T3 (es) | 2009-07-24 |
| TW200801515A (en) | 2008-01-01 |
| ATE431558T1 (de) | 2009-05-15 |
| EP2322936A1 (en) | 2011-05-18 |
| EP2339349A1 (en) | 2011-06-29 |
| WO2007044094A1 (en) | 2007-04-19 |
| KR101375552B1 (ko) | 2014-03-24 |
| US20180024146A1 (en) | 2018-01-25 |
| TW201413246A (zh) | 2014-04-01 |
| EP2339349B1 (en) | 2016-08-17 |
| JP2009511905A (ja) | 2009-03-19 |
| EP2317321A1 (en) | 2011-05-04 |
| DE602006006855D1 (de) | 2009-06-25 |
| ES2477284T3 (es) | 2014-07-16 |
| CA2625300C (en) | 2018-01-02 |
| ES2588376T3 (es) | 2016-11-02 |
| EP2031398A1 (en) | 2009-03-04 |
| KR20080066785A (ko) | 2008-07-16 |
| JP4908514B2 (ja) | 2012-04-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2412268T3 (es) | Alteraciones específicas de la Enfermedad de Alzheimer de la relación de fosforilación ERK1/ERK2 como biomarcadores moleculares específicos de la Enfermedad de Alzheimer (ADSMB) | |
| US9797913B2 (en) | Alzheimer's disease-specific alterations of the ERK1/ERK2 phosphorylation ratio-alzheimer's disease-specific molecular biomarkers (ADSMB) | |
| CN101322032A (zh) | 阿耳茨海默病特异性的erk1/erk2磷酸化比率改变-阿耳茨海默病特异性分子生物标记(adsmb) | |
| JP2008520203A (ja) | アルツハイマー病の診断および治療のためのホスファターゼ２ａ（ｐｐ２ａ）の異常 | |
| US9518995B2 (en) | FKBP52-Tau interaction as a novel therapeutical target for treating the neurological disorders involving Tau dysfunction | |
| EP1934618B1 (en) | Alzheimer's disease-specific alterations of the erk1/erk2 phosphorylation ratio-alzheimer's disease-specific molecular biomarkers (adsmb) | |
| JP6013184B2 (ja) | アルツハイマー病末梢細胞におけるｐｋｃアイソザイムプロセッシングの異常変化 | |
| WO2007043998A1 (en) | Alzheimer’s disease-specific alterations of the erk1/erk2 phosphorylation ratio | |
| EP2263090A1 (en) | Alzheimer's disease-specific alterations of the erk1/erk2 phosphorylation ratio-alzheimer's disease-specific molecular biomarkers (adsmb) | |
| US20080221042A1 (en) | Alzheimer's disease-specific alterations of the ERK1/ERK2 Phosphorylation ratio-Alzheimer's disease-specific molecular biomarkers (ADSMB) | |
| ES2498465A1 (es) | Método de diagnóstico y/o pronóstico de la enfermedad de alzheimer |