DE69736976T2 - Mit Alzheimer Krankheit verknüpften Verfahren zur Diagnose, zur Herstellung von Medikamenten und zum Screenen von Substanzen sowie aus Beta-Amyloid abgeleiteten Peptiden - Google Patents
Mit Alzheimer Krankheit verknüpften Verfahren zur Diagnose, zur Herstellung von Medikamenten und zum Screenen von Substanzen sowie aus Beta-Amyloid abgeleiteten Peptiden Download PDFInfo
- Publication number
- DE69736976T2 DE69736976T2 DE69736976T DE69736976T DE69736976T2 DE 69736976 T2 DE69736976 T2 DE 69736976T2 DE 69736976 T DE69736976 T DE 69736976T DE 69736976 T DE69736976 T DE 69736976T DE 69736976 T2 DE69736976 T2 DE 69736976T2
- Authority
- DE
- Germany
- Prior art keywords
- amyloid
- growth factor
- protein
- nerve growth
- peptide
- 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.)
- Expired - Fee Related
Links
- 108010090849 Amyloid beta-Peptides Proteins 0.000 title claims abstract description 182
- 102000013455 Amyloid beta-Peptides Human genes 0.000 title claims abstract description 182
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 67
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 57
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 15
- 239000003814 drug Substances 0.000 title claims description 5
- 229940079593 drug Drugs 0.000 title description 2
- 238000012216 screening Methods 0.000 title description 2
- 210000002752 melanocyte Anatomy 0.000 claims abstract description 108
- 102000007339 Nerve Growth Factor Receptors Human genes 0.000 claims abstract description 40
- 108010032605 Nerve Growth Factor Receptors Proteins 0.000 claims abstract description 40
- 238000000034 method Methods 0.000 claims abstract description 38
- 108010025020 Nerve Growth Factor Proteins 0.000 claims description 79
- 102000015336 Nerve Growth Factor Human genes 0.000 claims description 76
- 210000004027 cell Anatomy 0.000 claims description 75
- 229940053128 nerve growth factor Drugs 0.000 claims description 75
- 230000006907 apoptotic process Effects 0.000 claims description 43
- 230000004913 activation Effects 0.000 claims description 38
- 108090000623 proteins and genes Proteins 0.000 claims description 31
- 102000004169 proteins and genes Human genes 0.000 claims description 29
- 238000004458 analytical method Methods 0.000 claims description 27
- 230000001965 increasing effect Effects 0.000 claims description 27
- 239000000126 substance Substances 0.000 claims description 27
- 239000012634 fragment Substances 0.000 claims description 25
- 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 description 22
- 210000003169 central nervous system Anatomy 0.000 claims description 19
- 102000005962 receptors Human genes 0.000 claims description 18
- 108020003175 receptors Proteins 0.000 claims description 18
- 108010064397 amyloid beta-protein (1-40) Proteins 0.000 claims description 17
- 108700000707 bcl-2-Associated X Proteins 0.000 claims description 17
- 102000055102 bcl-2-Associated X Human genes 0.000 claims description 17
- 238000012360 testing method Methods 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 13
- 150000001413 amino acids Chemical group 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 230000004770 neurodegeneration Effects 0.000 claims description 11
- 206010012289 Dementia Diseases 0.000 claims description 10
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 10
- 230000001419 dependent effect Effects 0.000 claims description 8
- 238000009395 breeding Methods 0.000 claims description 7
- 230000001488 breeding effect Effects 0.000 claims description 7
- 230000014509 gene expression Effects 0.000 claims description 7
- 210000003061 neural cell Anatomy 0.000 claims description 7
- 238000004113 cell culture Methods 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 238000005259 measurement Methods 0.000 claims description 4
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 claims description 4
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 claims description 3
- 230000002596 correlated effect Effects 0.000 claims description 3
- 210000002950 fibroblast Anatomy 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 108020004999 messenger RNA Proteins 0.000 claims description 3
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 2
- 230000005855 radiation Effects 0.000 claims description 2
- 238000001262 western blot Methods 0.000 claims description 2
- 230000010261 cell growth Effects 0.000 claims 2
- 238000003860 storage Methods 0.000 claims 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 230000003247 decreasing effect Effects 0.000 claims 1
- 238000004321 preservation Methods 0.000 claims 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 abstract description 7
- 210000000933 neural crest Anatomy 0.000 abstract description 2
- 102100038313 Transcription factor E2-alpha Human genes 0.000 description 77
- 210000002569 neuron Anatomy 0.000 description 34
- 235000018102 proteins Nutrition 0.000 description 24
- FEWOUVRMGWFWIH-ILZZQXMPSA-N amyloid-beta polypeptide 40 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)=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 FEWOUVRMGWFWIH-ILZZQXMPSA-N 0.000 description 14
- 238000000338 in vitro Methods 0.000 description 12
- 125000003275 alpha amino acid group Chemical group 0.000 description 10
- 230000030833 cell death Effects 0.000 description 10
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 10
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 230000001537 neural effect Effects 0.000 description 9
- 230000004083 survival effect Effects 0.000 description 9
- 102000001189 Cyclic Peptides Human genes 0.000 description 8
- 108010069514 Cyclic Peptides Proteins 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 235000001014 amino acid Nutrition 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 7
- 230000004071 biological effect Effects 0.000 description 7
- 230000007423 decrease Effects 0.000 description 7
- 238000003745 diagnosis Methods 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 125000000539 amino acid group Chemical group 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- 230000001629 suppression Effects 0.000 description 5
- 230000001960 triggered effect Effects 0.000 description 5
- 230000002159 abnormal effect Effects 0.000 description 4
- 230000003213 activating effect Effects 0.000 description 4
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000011005 laboratory method Methods 0.000 description 4
- 239000006166 lysate Substances 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 210000005036 nerve Anatomy 0.000 description 4
- 230000000750 progressive effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 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 3
- 101100222854 Bacillus subtilis (strain 168) czcO gene Proteins 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- 101100537961 Methanosarcina mazei (strain ATCC BAA-159 / DSM 3647 / Goe1 / Go1 / JCM 11833 / OCM 88) trkA2 gene Proteins 0.000 description 3
- 102000007072 Nerve Growth Factors Human genes 0.000 description 3
- 208000028389 Nerve injury Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000001594 aberrant effect Effects 0.000 description 3
- 238000001574 biopsy Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000008764 nerve damage Effects 0.000 description 3
- 210000001982 neural crest cell Anatomy 0.000 description 3
- 230000016273 neuron death Effects 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 239000012679 serum free medium Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 3
- 101150025395 trkA gene Proteins 0.000 description 3
- 101150113435 trkA1 gene Proteins 0.000 description 3
- 108010039627 Aprotinin Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 2
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 2
- 206010064571 Gene mutation Diseases 0.000 description 2
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 2
- 108010061306 Lipoprotein Receptors Proteins 0.000 description 2
- 102000011965 Lipoprotein Receptors Human genes 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 206010033799 Paralysis Diseases 0.000 description 2
- 239000012083 RIPA buffer Substances 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000001640 apoptogenic effect Effects 0.000 description 2
- 238000003782 apoptosis assay Methods 0.000 description 2
- 229960004405 aprotinin Drugs 0.000 description 2
- 238000000211 autoradiogram Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 229960003964 deoxycholic acid Drugs 0.000 description 2
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 230000002900 effect on cell Effects 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229960000890 hydrocortisone Drugs 0.000 description 2
- 230000008105 immune reaction Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
- 230000000977 initiatory 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
- 230000003993 interaction Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000007830 nerve conduction Effects 0.000 description 2
- 238000007427 paired t-test Methods 0.000 description 2
- 230000007310 pathophysiology Effects 0.000 description 2
- 230000007505 plaque formation Effects 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000005522 programmed cell death Effects 0.000 description 2
- 238000007390 skin biopsy Methods 0.000 description 2
- 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 2
- 238000012916 structural analysis Methods 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 101150037123 APOE gene Proteins 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 206010002942 Apathy Diseases 0.000 description 1
- 102000013918 Apolipoproteins E Human genes 0.000 description 1
- 108010025628 Apolipoproteins E Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000024806 Brain atrophy Diseases 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 102000009016 Cholera Toxin Human genes 0.000 description 1
- 108010049048 Cholera Toxin Proteins 0.000 description 1
- 208000011990 Corticobasal Degeneration Diseases 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 1
- 101100216294 Danio rerio apoeb gene Proteins 0.000 description 1
- AHCYMLUZIRLXAA-SHYZEUOFSA-N Deoxyuridine 5'-triphosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 AHCYMLUZIRLXAA-SHYZEUOFSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 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
- 102000000853 LDL receptors Human genes 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 101150064037 NGF gene Proteins 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 208000014060 Niemann-Pick disease Diseases 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 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 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical compound IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000006933 amyloid-beta aggregation Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 238000010420 art technique Methods 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 210000002932 cholinergic neuron Anatomy 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 210000001787 dendrite Anatomy 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 208000015756 familial Alzheimer disease Diseases 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
- 230000006870 function Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 230000012447 hatching Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 210000005014 lower spinal cord Anatomy 0.000 description 1
- 230000036244 malformation Effects 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000002241 neurite Anatomy 0.000 description 1
- 230000019581 neuron apoptotic process Effects 0.000 description 1
- 230000008555 neuronal activation Effects 0.000 description 1
- 230000009223 neuronal apoptosis Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000000508 neurotrophic effect Effects 0.000 description 1
- 239000003900 neurotrophic factor Substances 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000007388 punch biopsy Methods 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 108010005584 serpin-enzyme complex receptor Proteins 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 210000004511 skin melanocyte Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 229940035722 triiodothyronine Drugs 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0815—Tripeptides with the first amino acid being basic
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4711—Alzheimer's disease; Amyloid plaque core protein
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/48—Nerve growth factor [NGF]
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/28—Neurological disorders
- G01N2800/2814—Dementia; Cognitive disorders
- G01N2800/2821—Alzheimer
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Neurology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Psychiatry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US625765 | 1984-06-28 | ||
| US62576596A | 1996-03-29 | 1996-03-29 | |
| PCT/US1997/004966 WO1997037228A1 (en) | 1996-03-29 | 1997-03-28 | Methods for diagnosing and treating alzheimer's disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69736976D1 DE69736976D1 (de) | 2007-01-04 |
| DE69736976T2 true DE69736976T2 (de) | 2007-10-18 |
Family
ID=24507498
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69736976T Expired - Fee Related DE69736976T2 (de) | 1996-03-29 | 1997-03-28 | Mit Alzheimer Krankheit verknüpften Verfahren zur Diagnose, zur Herstellung von Medikamenten und zum Screenen von Substanzen sowie aus Beta-Amyloid abgeleiteten Peptiden |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US6242416B1 (enExample) |
| EP (1) | EP0890105B1 (enExample) |
| JP (1) | JP2000507828A (enExample) |
| AT (1) | ATE346303T1 (enExample) |
| AU (1) | AU719038B2 (enExample) |
| CA (1) | CA2250075C (enExample) |
| DE (1) | DE69736976T2 (enExample) |
| WO (1) | WO1997037228A1 (enExample) |
Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6867179B1 (en) | 1994-08-31 | 2005-03-15 | Trustees Of Boston University | Methods of inducing hair growth and coloration |
| US7196055B2 (en) * | 1994-08-31 | 2007-03-27 | Trustees Of Boston University | Inhibition of apoptosis in keratinocytes by a ligand of p75 nerve growth factor receptor |
| EP0890105B1 (en) | 1996-03-29 | 2006-11-22 | The Trustees Of Boston University | Methods related to Alzheimer's disease for diagnosis, manufacture of medicaments and screening of substances and beta-amyloid related peptides |
| EP1207897A2 (en) * | 1999-08-09 | 2002-05-29 | Tripep Ab | Pharmaceutical compositions containing tripeptides |
| US6258932B1 (en) * | 1999-08-09 | 2001-07-10 | Tripep Ab | Peptides that block viral infectivity and methods of use thereof |
| KR20020007432A (ko) * | 2000-07-13 | 2002-01-29 | 박현석 | 멜라노트랜스페린에 대한 단클론 항체를 유효성분으로포함하는 알츠하이머병의 진단시약 |
| US6593455B2 (en) * | 2001-08-24 | 2003-07-15 | Tripep Ab | Tripeptide amides that block viral infectivity and methods of use thereof |
| US6455670B1 (en) * | 2001-09-06 | 2002-09-24 | Tripep Ab | Pentamer peptide amide, ALGPG-NH2, that inhibits viral infectivity and methods of use thereof |
| EP1436317A1 (en) * | 2001-09-19 | 2004-07-14 | Tripep Ab | Molecules that block viral infectivity and methods of use thereof |
| AUPS230702A0 (en) * | 2002-05-14 | 2002-06-13 | Walter And Eliza Hall Institute Of Medical Research, The | A method of treatment |
| US20050096319A1 (en) * | 2003-02-21 | 2005-05-05 | Balzarini Jan M.R. | Identification of compounds that inhibit replication of human immunodeficiency virus |
| HK1079984A1 (zh) * | 2003-02-21 | 2006-04-21 | Tripep Ab | 抑制hiv复制的甘氨酰胺衍生物 |
| WO2004087744A2 (en) * | 2003-03-28 | 2004-10-14 | Intellectual Property Consulting Inc. | Composition and method for nerve regeneration |
| PL1625150T3 (pl) | 2003-05-08 | 2007-05-31 | Dsm Ip Assets Bv | Tripeptydy i ich pochodne do stosowania w kosmetyce w celu poprawy struktury skóry |
| EP1718324A4 (en) * | 2003-06-11 | 2009-07-15 | Socratech L L C | A SOLUBLE PROTEIN RELATED TO THE LOW DENSITY LIPOPROTEIN RECEPTOR BINDS DIRECTLY TO THE ALZHEIMER BETA AMYLOID PEPTIDE |
| EP1500399A1 (en) * | 2003-07-24 | 2005-01-26 | Institut Pasteur | Active or passive immunization against proapoptotic neurotrophins for the treatment or prevention of neurodegenerative deseases |
| US20110230479A1 (en) * | 2005-04-15 | 2011-09-22 | Longo Frank M | Neurotrophin mimetics and uses thereof |
| EP1871420A4 (en) * | 2005-04-15 | 2010-09-22 | Univ North Carolina | PROCESS FOR ENABLING CELL SURVIVAL VIA NEUROTROPHINE MIMETICS |
| WO2006116400A2 (en) * | 2005-04-27 | 2006-11-02 | Massachusetts Institute Of Technology | Promoter engineering and genetic control |
| WO2008050754A1 (fr) * | 2006-10-23 | 2008-05-02 | National University Corporation Nagoya University | Inhibiteur de l'oxydation intracérébrale et utilisation de celui-ci |
| BRPI0921837A2 (pt) | 2008-11-25 | 2016-01-12 | Biogen Idec Inc | anticorpos isolados ou fragmentos de antígeno de ligação dos mesmos que podem se ligar especificamente a um polipeptídio dr6, métodos in vitro de promover a sobrevivência de uma célula do sistema nervoso, usos de um antagonista dr6 e métodos in vitro de inibir a ligação de dr6 com p75 |
| TW201034684A (en) * | 2009-02-18 | 2010-10-01 | Genentech Inc | Method for inhibiting neurodegeneration |
| US9458427B2 (en) * | 2009-08-07 | 2016-10-04 | Case Western Reserve University | IFNγR2 compositions and methods of inhibiting neuronal cell death |
| ES2712752T3 (es) | 2009-11-12 | 2019-05-14 | Pharmatrophix Inc | Formas cristalinas de compuestos miméticos de neurotrofina y sus sales |
| CN102612374A (zh) * | 2009-11-12 | 2012-07-25 | 霍夫曼-拉罗奇有限公司 | 提升树突棘密度的方法 |
| US10273219B2 (en) | 2009-11-12 | 2019-04-30 | Pharmatrophix, Inc. | Crystalline forms of neurotrophin mimetic compounds and their salts |
| US9216217B2 (en) * | 2010-03-03 | 2015-12-22 | The University Of British Columbia | Oligomer-specific amyloid beta epitope and antibodies |
| AU2013205000B2 (en) * | 2010-03-03 | 2015-05-28 | The University Of British Columbia | Oligomer-specific amyloid beta epitope and antibodies |
| ES2628596T3 (es) * | 2010-11-29 | 2017-08-03 | Akershus Universitetssykehus | Procedimientos y composiciones para monitorizar la actividad fagocítica |
| US20140235496A1 (en) * | 2011-10-05 | 2014-08-21 | Blanchette Rockefeller Neurosciences Drive | Stimulus-elicited genomic profile markers of a neurodegenerative condition |
| WO2013082045A1 (en) * | 2011-11-28 | 2013-06-06 | Buck Institute For Age Research | Netrin loop peptide mimetics and uses thereof |
| GB2516045A (en) * | 2013-07-09 | 2015-01-14 | Neuro Bio Ltd | Neurodegenerative disorders |
| EP2950095B1 (en) | 2014-05-28 | 2018-08-29 | Technische Universität Dresden | Cell-based assay and screening methods for modulators of p75NTR signaling |
| CN116626310A (zh) * | 2017-03-06 | 2023-08-22 | 刘军 | Aβ-诱导的损伤的抑制或减轻药剂 |
| CA3070446A1 (en) | 2017-07-25 | 2019-01-31 | Immutics, Inc. | Treating cancer by blocking the interaction of tim-3 and its ligand |
| JP6359160B2 (ja) * | 2017-07-25 | 2018-07-18 | 株式会社Ｍｃｂｉ | 認知機能障害疾患のバイオマーカーおよび該バイオマーカーを用いる認知機能障害疾患の検出方法 |
| CN120058944A (zh) | 2019-01-30 | 2025-05-30 | 真和制药有限公司 | 抗gal3抗体及其用途 |
| EP4157338A4 (en) | 2020-05-26 | 2024-11-13 | TrueBinding, Inc. | METHOD FOR TREATING INFLAMMATORY DISEASES BY GALECTIN-3 BLOCKING |
| CN119661638B (zh) * | 2024-11-22 | 2025-07-18 | 象山县第一人民医院医疗健康集团(宁波市第四医院、宁波市第四医院医院管理研究所) | 一种修复神经损伤的多肽、制备方法及其应用 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5288641A (en) | 1984-06-04 | 1994-02-22 | Arch Development Corporation | Herpes Simplex virus as a vector |
| US4918405A (en) * | 1988-10-26 | 1990-04-17 | Hewlett-Packard Company | Signal generator utilizing a combined phase locked and frequency locked loop |
| FR2662355B1 (fr) * | 1990-05-22 | 1994-11-10 | Sanofi Sa | Utilisation de la 1-[2-(2-naphtyl)ethyl]-4-(3-trifluoromethylphenyl)-1,2,3,6-tetrahydropyridine pour la preparation de medicaments destines au traitement de troubles cerebraux et neuronaux. |
| US5618822A (en) * | 1990-05-23 | 1997-04-08 | Sanofi | N-substituted trifluoromethylphenyltetrahydropyridines, process for the preparation thereof, intermediates in said process and pharmaceutical compositions containing them |
| IL101661A (en) * | 1991-04-23 | 1998-02-08 | Regeneron Pharma | Method for detecting, identifying or measuring agents having neurotrophin activity |
| TW327194B (en) * | 1992-05-01 | 1998-02-21 | American Cyanamid Co | Novel amyloid precursor proteins and methods of using same |
| US5976816A (en) | 1993-05-03 | 1999-11-02 | The United States Of America As Represented By The Department Of Health And Human Services | Cell tests for alzheimer's disease |
| GB9402331D0 (en) * | 1994-02-07 | 1994-03-30 | Univ Mcgill | Nerve growth factor structural analogs and their uses |
| US5576209A (en) | 1994-10-24 | 1996-11-19 | The Regents Of The University Of California | Method for increasing the resistance of neural cells to β-amyloid peptide toxicity |
| EP0890105B1 (en) * | 1996-03-29 | 2006-11-22 | The Trustees Of Boston University | Methods related to Alzheimer's disease for diagnosis, manufacture of medicaments and screening of substances and beta-amyloid related peptides |
-
1997
- 1997-03-28 EP EP97919932A patent/EP0890105B1/en not_active Expired - Lifetime
- 1997-03-28 JP JP9535410A patent/JP2000507828A/ja not_active Ceased
- 1997-03-28 DE DE69736976T patent/DE69736976T2/de not_active Expired - Fee Related
- 1997-03-28 AU AU24245/97A patent/AU719038B2/en not_active Ceased
- 1997-03-28 CA CA002250075A patent/CA2250075C/en not_active Expired - Fee Related
- 1997-03-28 WO PCT/US1997/004966 patent/WO1997037228A1/en not_active Ceased
- 1997-03-28 AT AT97919932T patent/ATE346303T1/de not_active IP Right Cessation
-
1998
- 1998-09-29 US US09/163,095 patent/US6242416B1/en not_active Expired - Fee Related
-
2001
- 2001-05-29 US US09/866,898 patent/US6696303B2/en not_active Expired - Fee Related
-
2004
- 2004-02-24 US US10/785,924 patent/US20040254110A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| DE69736976D1 (de) | 2007-01-04 |
| JP2000507828A (ja) | 2000-06-27 |
| US20040254110A1 (en) | 2004-12-16 |
| CA2250075C (en) | 2008-06-10 |
| EP0890105A1 (en) | 1999-01-13 |
| US20020051988A1 (en) | 2002-05-02 |
| ATE346303T1 (de) | 2006-12-15 |
| AU2424597A (en) | 1997-10-22 |
| CA2250075A1 (en) | 1997-10-09 |
| US6696303B2 (en) | 2004-02-24 |
| AU719038B2 (en) | 2000-05-04 |
| US6242416B1 (en) | 2001-06-05 |
| EP0890105B1 (en) | 2006-11-22 |
| WO1997037228A1 (en) | 1997-10-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69736976T2 (de) | Mit Alzheimer Krankheit verknüpften Verfahren zur Diagnose, zur Herstellung von Medikamenten und zum Screenen von Substanzen sowie aus Beta-Amyloid abgeleiteten Peptiden | |
| DE60016227T2 (de) | Globularer aufbau vom amyloid-beta- protein und deren verwendungen | |
| DE69333144T2 (de) | Verfahren zur Identifizierung von Hemmstoffe der Produktion des beta-Amyloidpeptids | |
| DE69836740T2 (de) | Amyloid beta protein (globulärer aufbau und seine verwendung) | |
| DE69031168T2 (de) | Verwendung von IGF1 oder IGF2 zur Herstellung eines Medikaments für die Behandlung von amyotrophischen Lateralsklerose | |
| DE69333225T2 (de) | Verfahren und zusammensetzungen zur beobachtung der zellulären verarbeitung von beta-amyloid-vorläuferproteinen | |
| DE69125523T2 (de) | Verwendung eines Modulators der Proteinphosphorylierung zur Behandlung der Amyloidosis in Zusammenhang mit der Alzheimerschen Krankheit | |
| DE69233195T2 (de) | Verwendung von app-modulatoren zur herstellung eines medikamentes zur behandlung der amyloidose | |
| DE69535462T2 (de) | Zusammensetzung und Verfahren zur Inhibition der Filamentbildung des Amyloid-Betaproteins und seiner Neutotoxizität | |
| DE69435088T2 (de) | Therapeutische und diagnostische mittel für die amyloidosis | |
| DE69736712T2 (de) | Verfahren zur milderung von neuropatischen schmerz mit prosaposin verwandten peptiden | |
| DE69703449T2 (de) | Neuroaktive peptide | |
| DE69633336T2 (de) | Zusamenzetzung enthaltend einen inhibitor des myelin assoziierten glycoproteins (mag), welcher einer veränderten oder mutierten form von mag enthält | |
| DE68923362T2 (de) | Wachstumsregelfaktoren für neuriten. | |
| DE69738331T2 (de) | Therapeutische anwendungen von laminin und von proteinfragmenten die von laminin abgeleitet sind | |
| Liberini et al. | Long-term protective effects of human recombinant nerve growth factor and monosialoganglioside GM1 treatment on primate nucleus basalis cholinergic neurons after neocortical infarction | |
| WO1994009808A1 (en) | Substances having the growth-promoting effect of amyloid precursor protein | |
| DE69433243T2 (de) | Verwendunf von ApoE zum Binden von TAU und MAP2c Proteinen und zur Behandlung von Alzheimer's Krankheit | |
| Cunningham et al. | Calreticulin binding and other biological activities of survival peptide Y-P30 including effects of systemic treatment of rats | |
| DE60124915T2 (de) | Synthetische peptide gegen neurologische krankheiten | |
| DE69922535T2 (de) | Komplex, bestehend aus einem chaperon und beta-amyloidprotein sowie verfahren, die diesen komplex benutzen | |
| US20100197740A1 (en) | Method of Screening Compounds Having Anti-Amyloid Properties | |
| DE69231930T2 (de) | Verfahren zur behandlung von erkrankungen motorischer neuronen durch mitglieder der bdnf/nt-3/ngf-familie | |
| EP0862460A1 (en) | Methods of reducing apolipoprotein e4-induced inhibition of neuron remodeling | |
| Naffah-Mazzacoratti et al. | Growth-associated phosphoprotein expression is increased in the supragranular regions of the dentate gyrus following pilocarpine-induced seizures in rats |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |