TWI448688B - 以阿茲海默症特異性之ｅｒｋ１／ｅｒｋ２磷酸化比率的變化作為阿茲海默症特異性的分子生物標記 - Google Patents
以阿茲海默症特異性之ｅｒｋ１／ｅｒｋ２磷酸化比率的變化作為阿茲海默症特異性的分子生物標記 Download PDFInfo
- Publication number
- TWI448688B TWI448688B TW095137389A TW95137389A TWI448688B TW I448688 B TWI448688 B TW I448688B TW 095137389 A TW095137389 A TW 095137389A TW 95137389 A TW95137389 A TW 95137389A TW I448688 B TWI448688 B TW I448688B
- Authority
- TW
- Taiwan
- Prior art keywords
- alzheimer
- disease
- cells
- cell
- phosphorylated
- Prior art date
Links
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 220
- 239000000090 biomarker Substances 0.000 title claims description 85
- 230000026731 phosphorylation Effects 0.000 title claims description 37
- 238000006366 phosphorylation reaction Methods 0.000 title claims description 37
- 230000004075 alteration Effects 0.000 title description 2
- 101100226056 Dictyostelium discoideum erkA gene Proteins 0.000 title 1
- 101100226058 Dictyostelium discoideum erkB gene Proteins 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 127
- 102000043136 MAP kinase family Human genes 0.000 claims abstract description 76
- 108091054455 MAP kinase family Proteins 0.000 claims abstract description 76
- 108090000315 Protein Kinase C Proteins 0.000 claims abstract description 68
- 102000003923 Protein Kinase C Human genes 0.000 claims abstract description 68
- 239000012190 activator Substances 0.000 claims abstract description 55
- 150000001875 compounds Chemical class 0.000 claims abstract description 55
- 238000012360 testing method Methods 0.000 claims abstract description 40
- 238000012216 screening Methods 0.000 claims abstract description 25
- 210000004027 cell Anatomy 0.000 claims description 203
- 101150018665 MAPK3 gene Proteins 0.000 claims description 56
- 101150024075 Mapk1 gene Proteins 0.000 claims description 43
- 108090000623 proteins and genes Proteins 0.000 claims description 42
- 102000004169 proteins and genes Human genes 0.000 claims description 40
- 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 32
- 238000003556 assay Methods 0.000 claims description 32
- 238000004458 analytical method Methods 0.000 claims description 25
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 22
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 claims description 21
- 229940088597 hormone Drugs 0.000 claims description 21
- 239000005556 hormone Substances 0.000 claims description 21
- 238000003018 immunoassay Methods 0.000 claims description 20
- 238000001262 western blot Methods 0.000 claims description 15
- 229960005520 bryostatin Drugs 0.000 claims description 14
- MJQUEDHRCUIRLF-TVIXENOKSA-N bryostatin 1 Chemical compound C([C@@H]1CC(/[C@@H]([C@@](C(C)(C)/C=C/2)(O)O1)OC(=O)/C=C/C=C/CCC)=C\C(=O)OC)[C@H]([C@@H](C)O)OC(=O)C[C@H](O)C[C@@H](O1)C[C@H](OC(C)=O)C(C)(C)[C@]1(O)C[C@@H]1C\C(=C\C(=O)OC)C[C@H]\2O1 MJQUEDHRCUIRLF-TVIXENOKSA-N 0.000 claims description 14
- MUIWQCKLQMOUAT-AKUNNTHJSA-N bryostatin 20 Natural products COC(=O)C=C1C[C@@]2(C)C[C@]3(O)O[C@](C)(C[C@@H](O)CC(=O)O[C@](C)(C[C@@]4(C)O[C@](O)(CC5=CC(=O)O[C@]45C)C(C)(C)C=C[C@@](C)(C1)O2)[C@@H](C)O)C[C@H](OC(=O)C(C)(C)C)C3(C)C MUIWQCKLQMOUAT-AKUNNTHJSA-N 0.000 claims description 14
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 14
- 230000002093 peripheral effect Effects 0.000 claims description 14
- 210000001626 skin fibroblast Anatomy 0.000 claims description 14
- 239000002609 medium Substances 0.000 claims description 13
- 210000002966 serum Anatomy 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 13
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 claims description 10
- 102000004190 Enzymes Human genes 0.000 claims description 9
- 108090000790 Enzymes Proteins 0.000 claims description 9
- 210000000601 blood cell Anatomy 0.000 claims description 9
- 229940088598 enzyme Drugs 0.000 claims description 9
- 210000004927 skin cell Anatomy 0.000 claims description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 8
- 239000012679 serum free medium Substances 0.000 claims description 8
- 108090000190 Thrombin Proteins 0.000 claims description 7
- 229960004072 thrombin Drugs 0.000 claims description 7
- 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 6
- 108010064733 Angiotensins Proteins 0.000 claims description 6
- 102000015427 Angiotensins Human genes 0.000 claims description 6
- PXGPLTODNUVGFL-UHFFFAOYSA-N prostaglandin F2alpha Natural products CCCCCC(O)C=CC1C(O)CC(O)C1CC=CCCCC(O)=O PXGPLTODNUVGFL-UHFFFAOYSA-N 0.000 claims description 6
- ZGVSETXHNHBTRK-UDJLNJFBSA-N solanine Chemical group O([C@H]1[C@@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@H](O)[C@@H](O)[C@H](C)O1)O)O[C@@H]1CC2=CC[C@H]3[C@@H]4C[C@@H]5N6C[C@@H](C)CC[C@@H]6[C@H]([C@@H]5[C@@]4(C)CC[C@@H]3[C@@]2(C)CC1)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O ZGVSETXHNHBTRK-UDJLNJFBSA-N 0.000 claims description 6
- 230000008859 change Effects 0.000 claims description 5
- 238000001114 immunoprecipitation Methods 0.000 claims description 5
- 238000003127 radioimmunoassay Methods 0.000 claims description 5
- 239000013543 active substance Substances 0.000 claims description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 4
- 238000012258 culturing Methods 0.000 claims description 4
- 238000000760 immunoelectrophoresis Methods 0.000 claims description 4
- 238000010166 immunofluorescence Methods 0.000 claims description 4
- 238000000099 in vitro assay Methods 0.000 claims description 4
- 238000009593 lumbar puncture Methods 0.000 claims description 4
- 238000002493 microarray Methods 0.000 claims description 4
- 238000003498 protein array Methods 0.000 claims description 4
- 102000044159 Ubiquitin Human genes 0.000 claims description 3
- 108090000848 Ubiquitin Proteins 0.000 claims description 3
- 238000003271 compound fluorescence assay Methods 0.000 claims description 3
- 238000002991 immunohistochemical analysis Methods 0.000 claims description 3
- 238000012921 fluorescence analysis Methods 0.000 claims description 2
- 210000000278 spinal cord Anatomy 0.000 claims 2
- 238000003491 array Methods 0.000 claims 1
- 238000005259 measurement Methods 0.000 claims 1
- 244000052769 pathogen Species 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 abstract description 5
- 210000002950 fibroblast Anatomy 0.000 description 47
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 29
- 239000008194 pharmaceutical composition Substances 0.000 description 29
- 201000010099 disease Diseases 0.000 description 28
- 239000000243 solution Substances 0.000 description 27
- 101800004538 Bradykinin Proteins 0.000 description 23
- 102400000967 Bradykinin Human genes 0.000 description 23
- 206010012289 Dementia Diseases 0.000 description 23
- 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 description 23
- 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 description 22
- 239000000203 mixture Substances 0.000 description 21
- 238000001514 detection method Methods 0.000 description 20
- 150000002611 lead compounds Chemical class 0.000 description 20
- 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 19
- 239000002953 phosphate buffered saline Substances 0.000 description 19
- 239000000523 sample Substances 0.000 description 19
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 230000003834 intracellular effect Effects 0.000 description 14
- 210000001519 tissue Anatomy 0.000 description 14
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 13
- 230000035945 sensitivity Effects 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
- 230000002265 prevention Effects 0.000 description 10
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 238000011888 autopsy Methods 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 8
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 8
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
- 229920002472 Starch Polymers 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 150000001413 amino acids Chemical class 0.000 description 8
- 235000011089 carbon dioxide Nutrition 0.000 description 8
- 238000012790 confirmation Methods 0.000 description 8
- 235000002639 sodium chloride Nutrition 0.000 description 8
- 239000008107 starch Substances 0.000 description 8
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 7
- 208000018737 Parkinson disease Diseases 0.000 description 7
- 108091000080 Phosphotransferase Proteins 0.000 description 7
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 7
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 7
- 239000004473 Threonine Substances 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 238000012417 linear regression Methods 0.000 description 7
- 238000010606 normalization Methods 0.000 description 7
- 102000020233 phosphotransferase Human genes 0.000 description 7
- 210000003491 skin Anatomy 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 235000019698 starch Nutrition 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 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 6
- 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
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 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 description 6
- 108010004977 Vasopressins Proteins 0.000 description 6
- 102000002852 Vasopressins Human genes 0.000 description 6
- 230000002159 abnormal effect Effects 0.000 description 6
- 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 description 6
- 239000011575 calcium Substances 0.000 description 6
- 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 6
- 239000012091 fetal bovine serum Substances 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000002736 nonionic surfactant Substances 0.000 description 6
- 229940049954 penicillin Drugs 0.000 description 6
- 229960005322 streptomycin Drugs 0.000 description 6
- 229960003726 vasopressin Drugs 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 5
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 5
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- 102000014384 Type C Phospholipases Human genes 0.000 description 5
- 108010079194 Type C Phospholipases Proteins 0.000 description 5
- 229940076850 Tyrosine phosphatase inhibitor Drugs 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 5
- 238000003745 diagnosis Methods 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol Substances OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 239000006166 lysate Substances 0.000 description 5
- 238000012544 monitoring process Methods 0.000 description 5
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 5
- 229960002920 sorbitol Drugs 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
- 208000023105 Huntington disease Diseases 0.000 description 4
- 239000000020 Nitrocellulose Substances 0.000 description 4
- 239000013504 Triton X-100 Substances 0.000 description 4
- 229920004890 Triton X-100 Polymers 0.000 description 4
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 4
- 210000000321 buccal mucosa cell Anatomy 0.000 description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 239000013592 cell lysate Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 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 4
- 229940079593 drug Drugs 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 229920001220 nitrocellulos Polymers 0.000 description 4
- 210000003296 saliva Anatomy 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 239000011550 stock solution Substances 0.000 description 4
- 102000013498 tau Proteins Human genes 0.000 description 4
- 108010026424 tau Proteins Proteins 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
- 210000002700 urine Anatomy 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 102000019058 Glycogen Synthase Kinase 3 beta Human genes 0.000 description 3
- 108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 150000001242 acetic acid derivatives Chemical class 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 230000005754 cellular signaling Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000002500 effect on skin Effects 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000007951 isotonicity adjuster Substances 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 230000007310 pathophysiology Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 3
- 201000000980 schizophrenia Diseases 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 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
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-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
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 102000004149 Annexin A2 Human genes 0.000 description 2
- 108090000668 Annexin A2 Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 101710105094 Cyclic AMP-responsive element-binding protein Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 208000031124 Dementia Alzheimer type Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- 239000012722 SDS sample buffer Substances 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 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
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229940045799 anthracyclines and related substance Drugs 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 229960002903 benzyl benzoate Drugs 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 235000001465 calcium Nutrition 0.000 description 2
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 150000001860 citric acid derivatives Chemical class 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000003759 clinical diagnosis Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000030609 dephosphorylation Effects 0.000 description 2
- 238000006209 dephosphorylation reaction Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000001177 diphosphate Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000007877 drug screening Methods 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 208000014674 injury Diseases 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
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000003226 mitogen Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- -1 phloem Natural products 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- 108091005981 phosphorylated proteins Proteins 0.000 description 2
- 230000000865 phosphorylative effect Effects 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- 230000009822 protein phosphorylation Effects 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- QWHKYVBQPAUEPF-IBGZPJMESA-N (2s)-2,3-dioctoxypropan-1-ol Chemical compound CCCCCCCCOC[C@H](CO)OCCCCCCCC QWHKYVBQPAUEPF-IBGZPJMESA-N 0.000 description 1
- JXWKLNIPHOFKQD-NSUPYGROSA-N (3s,8r,9s,10r,13s,14s,17s)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-3,17-diol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@]([C@H](C)CCCC(C)C)(O)[C@@]1(C)CC2 JXWKLNIPHOFKQD-NSUPYGROSA-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
- VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QGVLYPPODPLXMB-FYYCTCHMSA-N 4α-phorbol Chemical compound C1=C(CO)C[C@@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(O)C(C)(C)[C@H]3[C@@H]21 QGVLYPPODPLXMB-FYYCTCHMSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 102000002281 Adenylate kinase Human genes 0.000 description 1
- 108020000543 Adenylate kinase Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 1
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 1
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 1
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 1
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 1
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 1
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 1
- 240000003291 Armoracia rusticana Species 0.000 description 1
- 235000011330 Armoracia rusticana Nutrition 0.000 description 1
- 230000007324 Aβ metabolism Effects 0.000 description 1
- 108010051479 Bombesin Proteins 0.000 description 1
- 102000013585 Bombesin Human genes 0.000 description 1
- 208000024806 Brain atrophy Diseases 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 241000700670 Bryozoa Species 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 102100035882 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 102100025841 Cholecystokinin Human genes 0.000 description 1
- 101800001982 Cholecystokinin Proteins 0.000 description 1
- PHEDXBVPIONUQT-UHFFFAOYSA-N Cocarcinogen A1 Natural products CCCCCCCCCCCCCC(=O)OC1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(CO)=CC2C2C1(OC(C)=O)C2(C)C PHEDXBVPIONUQT-UHFFFAOYSA-N 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 240000002943 Elettaria cardamomum Species 0.000 description 1
- PLAPMLGJVGLZOV-UHFFFAOYSA-N Epi-orientin Natural products OC1C(O)C(O)C(CO)OC1C1=C(O)C=C(O)C2=C1OC(C=1C=C(O)C(O)=CC=1)=CC2=O PLAPMLGJVGLZOV-UHFFFAOYSA-N 0.000 description 1
- ZFDIRQKJPRINOQ-HWKANZROSA-N Ethyl crotonate Chemical compound CCOC(=O)\C=C\C ZFDIRQKJPRINOQ-HWKANZROSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 101710165567 Extracellular signal-regulated kinase 1 Proteins 0.000 description 1
- 101710165576 Extracellular signal-regulated kinase 2 Proteins 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors 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
- 206010018910 Haemolysis Diseases 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000849321 Homo sapiens Protein RRP5 homolog Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004195 Isomerases Human genes 0.000 description 1
- 108090000769 Isomerases Proteins 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical group NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 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
- IXAQOQZEOGMIQS-ORRYEOPJSA-N Lipoxin A Natural products CCCCCC(O)C=CC=C/C=C/C=C/C(O)C(O)CCCC(=O)O IXAQOQZEOGMIQS-ORRYEOPJSA-N 0.000 description 1
- PTNJRKBWIYNFSY-UHFFFAOYSA-N Lirinin-O-methyl-ether Natural products COc1ccc-2c(CC3N(C)CCc4cc(OC)c(OC)c-2c34)c1 PTNJRKBWIYNFSY-UHFFFAOYSA-N 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
- 241000187723 Micromonospora sp. Species 0.000 description 1
- 102100040243 Microtubule-associated protein tau Human genes 0.000 description 1
- 101710115937 Microtubule-associated protein tau Proteins 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
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 1
- 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 1
- 102100024192 Mitogen-activated protein kinase 3 Human genes 0.000 description 1
- 244000111261 Mucuna pruriens Species 0.000 description 1
- 235000006161 Mucuna pruriens Nutrition 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- RBVAFYCFAFADAG-UHFFFAOYSA-N Orientin Natural products OCC1OC(C(O)c2c(O)cc(O)c3C(=O)C=C(Oc23)c4ccc(O)c(O)c4)C(O)C1O RBVAFYCFAFADAG-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 229940122907 Phosphatase inhibitor Drugs 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
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 241001263603 Stellera Species 0.000 description 1
- 241001263604 Stellera chamaejasme Species 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 108010018242 Transcription Factor AP-1 Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- LQSNPVIQIPKOGP-UHFFFAOYSA-N UNPD159785 Natural products OC1C(O)C(O)C(CO)OC1OC1=C(O)C=C(O)C2=C1OC(C=1C=C(O)C(O)=CC=1)=CC2=O LQSNPVIQIPKOGP-UHFFFAOYSA-N 0.000 description 1
- OTTFLYUONKAFGT-UHFFFAOYSA-N UNPD66298 Natural products CC(=C)C12OC(O3)(C=4C=CC=CC=4)OC1C1C4OC4(CO)C(O)C(C(C(C)=C4)=O)(O)C4C31C(C)C2OC(=O)C=CC1=CC=CC=C1 OTTFLYUONKAFGT-UHFFFAOYSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 235000018936 Vitellaria paradoxa Nutrition 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- MMWCIQZXVOZEGG-HOZKJCLWSA-N [(1S,2R,3S,4S,5R,6S)-2,3,5-trihydroxy-4,6-diphosphonooxycyclohexyl] dihydrogen phosphate 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-HOZKJCLWSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000003942 amyloidogenic effect Effects 0.000 description 1
- 229960004543 anhydrous citric acid Drugs 0.000 description 1
- MMCPOSDMTGQNKG-UHFFFAOYSA-N anilinium chloride Chemical compound Cl.NC1=CC=CC=C1 MMCPOSDMTGQNKG-UHFFFAOYSA-N 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
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- FXICHSQUUNYSCS-UHFFFAOYSA-N azane;chlorobenzene Chemical compound N.ClC1=CC=CC=C1 FXICHSQUUNYSCS-UHFFFAOYSA-N 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000008238 biochemical pathway Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 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 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 235000005300 cardamomo Nutrition 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
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229940107137 cholecystokinin Drugs 0.000 description 1
- 150000001841 cholesterols Chemical class 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 150000001982 diacylglycerols Chemical class 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 229960001342 dinoprost Drugs 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- QVAZSFSQBKLKMP-UHFFFAOYSA-N dodecylazanium;propanoate Chemical compound CCC([O-])=O.CCCCCCCCCCCC[NH3+] QVAZSFSQBKLKMP-UHFFFAOYSA-N 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000003492 excitotoxic effect Effects 0.000 description 1
- 231100000063 excitotoxicity Toxicity 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 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
- 239000011544 gradient gel Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 108091008039 hormone receptors Proteins 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 238000010185 immunofluorescence analysis Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000037456 inflammatory mechanism Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 208000028867 ischemia Diseases 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
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 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-N lipoxin A4 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-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 150000007931 macrolactones Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000463 material 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
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 239000012120 mounting media Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- COFKFSSWMQHKMD-UHFFFAOYSA-N n,n-didecyldecan-1-amine Chemical compound CCCCCCCCCCN(CCCCCCCCCC)CCCCCCCCCC COFKFSSWMQHKMD-UHFFFAOYSA-N 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- PEFNSGRTCBGNAN-UHFFFAOYSA-N nephrocizin Natural products OC1C(O)C(O)C(CO)OC1OC1=CC(O)=C2C(=O)C=C(C=3C=C(O)C(O)=CC=3)OC2=C1 PEFNSGRTCBGNAN-UHFFFAOYSA-N 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- ZHALDANPYXAMJF-UHFFFAOYSA-N octadecanoate;tris(2-hydroxyethyl)azanium Chemical compound OCC[NH+](CCO)CCO.CCCCCCCCCCCCCCCCCC([O-])=O ZHALDANPYXAMJF-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 210000000196 olfactory nerve Anatomy 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- PLAPMLGJVGLZOV-VPRICQMDSA-N orientin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=C(O)C2=C1OC(C=1C=C(O)C(O)=CC=1)=CC2=O PLAPMLGJVGLZOV-VPRICQMDSA-N 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- QGVLYPPODPLXMB-QXYKVGAMSA-N phorbol Natural products C[C@@H]1[C@@H](O)[C@]2(O)[C@H]([C@H]3C=C(CO)C[C@@]4(O)[C@H](C=C(C)C4=O)[C@@]13O)C2(C)C QGVLYPPODPLXMB-QXYKVGAMSA-N 0.000 description 1
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 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
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- PXGPLTODNUVGFL-YNNPMVKQSA-N prostaglandin F2alpha Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O PXGPLTODNUVGFL-YNNPMVKQSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 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 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000037351 starvation Effects 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012089 stop solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 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
- 238000002560 therapeutic procedure Methods 0.000 description 1
- OTTFLYUONKAFGT-KSFWXGPWSA-N thymeleatoxin Chemical compound O([C@@H]1[C@H]([C@]23[C@H]4[C@](C(C(C)=C4)=O)(O)[C@H](O)[C@@]4(CO)O[C@H]4[C@@H]3[C@H]3O[C@@](O2)(O[C@]31C(C)=C)C=1C=CC=CC=1)C)C(=O)\C=C\C1=CC=CC=C1 OTTFLYUONKAFGT-KSFWXGPWSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- ZFDIRQKJPRINOQ-UHFFFAOYSA-N transbutenic acid ethyl ester Natural products CCOC(=O)C=CC ZFDIRQKJPRINOQ-UHFFFAOYSA-N 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000002525 ultrasonication Methods 0.000 description 1
- VLOPEOIIELCUML-UHFFFAOYSA-L vanadium(2+);sulfate Chemical compound [V+2].[O-]S([O-])(=O)=O VLOPEOIIELCUML-UHFFFAOYSA-L 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
- 150000003772 α-tocopherols Chemical class 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)
- Microbiology (AREA)
- Pathology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physiology (AREA)
- Hospice & Palliative Care (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Psychiatry (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 (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/246,524 US7595167B2 (en) | 2005-10-11 | 2005-10-11 | Alzheimer's disease-specific alterations of the Erk1/Erk2 phosphorylation ratio |
| PCT/US2005/036014 WO2007043998A1 (en) | 2005-10-11 | 2005-10-11 | Alzheimer’s disease-specific alterations of the erk1/erk2 phosphorylation ratio |
| 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) |
| PCT/US2006/037186 WO2007047029A2 (en) | 2005-10-11 | 2006-09-25 | Alzheimer's disease-specific alterations of the erk1/erk2 phosphorylation ratio as alzheimer's disease-specific molecular biomarkers (adsmb) |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW200801515A TW200801515A (en) | 2008-01-01 |
| TWI448688B true TWI448688B (zh) | 2014-08-11 |
Family
ID=37067652
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW102146766A TW201413246A (zh) | 2005-10-11 | 2006-10-11 | 含有診斷阿茲海默症之試劑的套組 |
| TW095137389A TWI448688B (zh) | 2005-10-11 | 2006-10-11 | 以阿茲海默症特異性之ｅｒｋ１／ｅｒｋ２磷酸化比率的變化作為阿茲海默症特異性的分子生物標記 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW102146766A TW201413246A (zh) | 2005-10-11 | 2006-10-11 | 含有診斷阿茲海默症之試劑的套組 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20180024146A1 (enExample) |
| EP (5) | EP2322936A1 (enExample) |
| JP (1) | JP4908514B2 (enExample) |
| KR (2) | KR20140002073A (enExample) |
| AT (1) | ATE431558T1 (enExample) |
| CA (1) | CA2625300C (enExample) |
| DE (1) | DE602006006855D1 (enExample) |
| ES (5) | ES2596881T3 (enExample) |
| TW (2) | TW201413246A (enExample) |
| WO (1) | WO2007044094A1 (enExample) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1385531B1 (en) | 2001-02-27 | 2008-05-07 | Blanchette Rockefeller Neurosciences Institute | Alzheimer's disease diagnosis based on mitogen-activated protein kinase phosphorylation |
| US6825229B2 (en) | 2002-03-07 | 2004-11-30 | Blanchette Rockefeller Neurosciences Institute | Methods for Alzheimer's Disease treatment and cognitive enhancement |
| US20050065205A1 (en) | 2002-03-07 | 2005-03-24 | Daniel Alkon | Methods for Alzheimer's disease treatment and cognitive enhance |
| TW201207390A (en) | 2004-05-18 | 2012-02-16 | Brni Neurosciences Inst | Method for screening agent for antidepressant activity |
| 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) |
| JP2009544753A (ja) * | 2006-07-28 | 2009-12-17 | 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 | 細胞成長、シナプスリモデリング及び長期記憶の固定を刺激する方法 |
| EP2121000B1 (en) | 2007-02-09 | 2015-09-23 | Blanchette Rockefeller Neurosciences, Institute | Therapeutic effects of bryostatins, bryologs, and other related substances on head trauma-induced memory impairment and brain injury |
| WO2010014588A1 (en) | 2008-07-28 | 2010-02-04 | Blanchette Rockefeller Neurosciences Institute | Stimulus-elicited genomic profile markers of alzheimer's disease |
| US8163800B2 (en) | 2008-07-28 | 2012-04-24 | Blanchette Rockefeller Neurosciences Institute | PKC-activating compounds for the treatment of neurodegenerative diseases |
| KR20110057188A (ko) * | 2008-08-27 | 2011-05-31 | 하. 룬트벡 아크티에 셀스카브 | 바이오마커 프로파일 측정 시스템 및 방법 |
| 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 |
| CA2776501C (en) | 2009-10-02 | 2022-04-19 | Blanchette Rockefeller Neurosciences Institute | Fibroblast growth patterns for diagnosis of alzheimer's disease |
| EP2707693B1 (en) * | 2011-05-12 | 2016-10-12 | Florin V. Chirila | Peripheral diagnostic methods for screening alzheimer's disease using beta amyloid and intercellular communication |
| WO2013071281A1 (en) | 2011-11-13 | 2013-05-16 | 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 |
| EP3090261B8 (en) * | 2014-01-03 | 2019-06-26 | The West Virginia University Board of Governors on behalf of West Virginia University | Convergence of aggregation rate with validated peripheral diagnostics for alzheimer's disease |
| WO2018183703A1 (en) | 2017-03-31 | 2018-10-04 | NeuroDiagnostics LLC | Lymphocyte-based morphometric test for alzheimer's disease |
| US20220211700A1 (en) * | 2019-05-23 | 2022-07-07 | 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 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002067764A2 (en) * | 2001-02-27 | 2002-09-06 | Blanchette Rockefeller Neurosciences Institute | Alzheimer's disease diagnosis based on mitogen-activated protein kinase phosphorylation |
Family Cites Families (8)
| 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 |
| 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 EP EP10011290A patent/EP2322936A1/en not_active Withdrawn
- 2006-09-25 JP JP2008535546A patent/JP4908514B2/ja not_active Expired - Fee Related
- 2006-09-25 EP EP10011288.7A patent/EP2339349B1/en active Active
- 2006-09-25 ES ES10011289.5T patent/ES2596881T3/es active Active
- 2006-09-25 CA CA2625300A patent/CA2625300C/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 EP EP10011289.5A patent/EP2322934B1/en active Active
- 2006-09-25 DE DE602006006855T patent/DE602006006855D1/de active Active
- 2006-09-25 ES ES06825096T patent/ES2323813T3/es active Active
- 2006-09-25 ES ES10011288.7T patent/ES2588376T3/es active Active
- 2006-09-25 ES ES08020258T patent/ES2412268T3/es active Active
- 2006-09-25 AT AT06825096T patent/ATE431558T1/de not_active IP Right Cessation
- 2006-09-25 KR KR1020137031223A patent/KR20140002073A/ko not_active Withdrawn
- 2006-09-25 EP EP08020258A patent/EP2031398B1/en 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
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002067764A2 (en) * | 2001-02-27 | 2002-09-06 | Blanchette Rockefeller Neurosciences Institute | Alzheimer's disease diagnosis based on mitogen-activated protein kinase phosphorylation |
Non-Patent Citations (1)
| Title |
|---|
| Zhao, WQ et al., "MAP kinase signaling cascade dysfunction specific to Alzheimer's disease in fibroblasts", NEUROBIOLOGY OF DISEASE, vol.11, no.1, p.166-183, 2002/10 * |
Also Published As
| Publication number | Publication date |
|---|---|
| ATE431558T1 (de) | 2009-05-15 |
| ES2596881T3 (es) | 2017-01-12 |
| CA2625300C (en) | 2018-01-02 |
| US20180024146A1 (en) | 2018-01-25 |
| TW201413246A (zh) | 2014-04-01 |
| EP2031398B1 (en) | 2013-02-13 |
| ES2477284T3 (es) | 2014-07-16 |
| EP2322936A1 (en) | 2011-05-18 |
| KR101375552B1 (ko) | 2014-03-24 |
| KR20140002073A (ko) | 2014-01-07 |
| JP2009511905A (ja) | 2009-03-19 |
| ES2412268T3 (es) | 2013-07-10 |
| CA2625300A1 (en) | 2007-04-26 |
| EP2317321B1 (en) | 2014-04-02 |
| ES2588376T3 (es) | 2016-11-02 |
| EP2322934A1 (en) | 2011-05-18 |
| ES2323813T3 (es) | 2009-07-24 |
| JP4908514B2 (ja) | 2012-04-04 |
| EP2339349B1 (en) | 2016-08-17 |
| KR20080066785A (ko) | 2008-07-16 |
| EP2317321A1 (en) | 2011-05-04 |
| EP2031398A1 (en) | 2009-03-04 |
| TW200801515A (en) | 2008-01-01 |
| EP2339349A1 (en) | 2011-06-29 |
| EP2322934B1 (en) | 2016-08-31 |
| DE602006006855D1 (de) | 2009-06-25 |
| WO2007044094A1 (en) | 2007-04-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101375552B1 (ko) | 알츠하이머병-특이적 분자 생체 지표(ａｄｓｍｂ)로서 ｅｒｋ1/ｅｒｋ2 포스포릴화비의 알츠하이머병-특이적 변화 | |
| US9797913B2 (en) | Alzheimer's disease-specific alterations of the ERK1/ERK2 phosphorylation ratio-alzheimer's disease-specific molecular biomarkers (ADSMB) | |
| US7595167B2 (en) | Alzheimer's disease-specific alterations of the Erk1/Erk2 phosphorylation ratio | |
| Mirzaei et al. | Upregulation of proteolytic pathways and altered protein biosynthesis underlie retinal pathology in a mouse model of Alzheimer’s disease | |
| Hartlage-Rübsamen et al. | A glutaminyl cyclase-catalyzed α-synuclein modification identified in human synucleinopathies | |
| Cao et al. | Pseudo-phosphorylation at AT8 epitopes regulates the tau truncation at aspartate 421 | |
| US9618511B2 (en) | Methods and compositions for treating alzheimer's disease | |
| 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 | |
| WO2007047029A2 (en) | Alzheimer's disease-specific alterations of the erk1/erk2 phosphorylation ratio as alzheimer's disease-specific molecular biomarkers (adsmb) | |
| WO2007043998A1 (en) | Alzheimer’s disease-specific alterations of the erk1/erk2 phosphorylation ratio | |
| JP2011516883A (ja) | Ｅｒｋ１／ｅｒｋ２のリン酸化比のアルツハイマー病特異的な変化―アルツハイマー病に特異的な分子バイオマーカー（ａｄｓｍｂ） | |
| RU2822602C1 (ru) | Синтетический тетрапептид haee и его производные, предназначенные для защиты функции нейронов человека | |
| khalaf Haroon et al. | Assessment of some neurological complexities in kidney failure disease: evaluation of neuroproteins and neuropeptides | |
| Chen et al. | Synergistic effects of hIAPP and Aβ1–42 impaired the olfactory function associated with the decline of adult neurogenesis in SVZ | |
| Caltagarone | Differential localization of Hic-5 and paxillin in the brain of Alzheimer's disease subjects | |
| KR20070084247A (ko) | 알츠하이머 질환의 진단 및 치료를 위한 포스파타제 2ａ(ｐｐ2ａ)의 비정상 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |