TWI453217B - 抗β類澱粉蛋白單株抗體 - Google Patents

Info

Publication number

TWI453217B

TWI453217B TW097122016A TW97122016A TWI453217B TW I453217 B TWI453217 B TW I453217B TW 097122016 A TW097122016 A TW 097122016A TW 97122016 A TW97122016 A TW 97122016A TW I453217 B TWI453217 B TW I453217B

Authority

TW

Taiwan

Prior art keywords

antibody

amyloid

seq

peptide

protein

Prior art date

2007-06-12

Links

• Espacenet
• Global Dossier
• Discuss

• 108090000765 processed proteins & peptides Proteins 0.000 claims description 485
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 243
• 230000027455 binding Effects 0.000 claims description 203
• 108090000623 proteins and genes Proteins 0.000 claims description 151
• 235000018102 proteins Nutrition 0.000 claims description 148
• 102000004169 proteins and genes Human genes 0.000 claims description 148
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 116
• 201000010099 disease Diseases 0.000 claims description 111
• 239000000203 mixture Substances 0.000 claims description 111
• 238000000034 method Methods 0.000 claims description 109
• 210000004556 brain Anatomy 0.000 claims description 83
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 69
• 239000012634 fragment Substances 0.000 claims description 67
• 239000000427 antigen Substances 0.000 claims description 57
• 108091007433 antigens Proteins 0.000 claims description 57
• 102000036639 antigens Human genes 0.000 claims description 57
• 235000001014 amino acid Nutrition 0.000 claims description 53
• 230000000890 antigenic effect Effects 0.000 claims description 53
• 150000001413 amino acids Chemical class 0.000 claims description 47
• 241000282414 Homo sapiens Species 0.000 claims description 46
• 229920001184 polypeptide Polymers 0.000 claims description 46
• 208000024827 Alzheimer disease Diseases 0.000 claims description 42
• 210000004027 cell Anatomy 0.000 claims description 37
• 208000002780 macular degeneration Diseases 0.000 claims description 36
• 230000015572 biosynthetic process Effects 0.000 claims description 35
• 238000011282 treatment Methods 0.000 claims description 35
• 206010002022 amyloidosis Diseases 0.000 claims description 32
• 102000013455 Amyloid beta-Peptides Human genes 0.000 claims description 30
• 108010090849 Amyloid beta-Peptides Proteins 0.000 claims description 30
• 230000000694 effects Effects 0.000 claims description 28
• 108091033319 polynucleotide Proteins 0.000 claims description 28
• 102000040430 polynucleotide Human genes 0.000 claims description 28
• 239000002157 polynucleotide Substances 0.000 claims description 28
• 229920002472 Starch Polymers 0.000 claims description 27
• 208000010877 cognitive disease Diseases 0.000 claims description 27
• 235000019698 starch Nutrition 0.000 claims description 27
• 239000008107 starch Substances 0.000 claims description 25
• 208000027061 mild cognitive impairment Diseases 0.000 claims description 23
• 150000001875 compounds Chemical class 0.000 claims description 20
• 125000003729 nucleotide group Chemical group 0.000 claims description 19
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 18
• 201000008319 inclusion body myositis Diseases 0.000 claims description 18
• 230000001225 therapeutic effect Effects 0.000 claims description 18
• 239000002773 nucleotide Substances 0.000 claims description 17
• 239000003814 drug Substances 0.000 claims description 16
• 208000009829 Lewy Body Disease Diseases 0.000 claims description 14
• 201000002832 Lewy body dementia Diseases 0.000 claims description 14
• 230000001149 cognitive effect Effects 0.000 claims description 14
• 238000012360 testing method Methods 0.000 claims description 14
• 239000000544 cholinesterase inhibitor Substances 0.000 claims description 12
• ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 claims description 12
• ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 claims description 11
• 206010012289 Dementia Diseases 0.000 claims description 10
• 239000003085 diluting agent Substances 0.000 claims description 10
• 239000003937 drug carrier Substances 0.000 claims description 9
• 238000006467 substitution reaction Methods 0.000 claims description 9
• 206010008111 Cerebral haemorrhage Diseases 0.000 claims description 8
• 206010033799 Paralysis Diseases 0.000 claims description 8
• 208000007660 Residual Neoplasm Diseases 0.000 claims description 8
• 229940088623 biologically active substance Drugs 0.000 claims description 8
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
• 230000000750 progressive effect Effects 0.000 claims description 8
• 206010065040 AIDS dementia complex Diseases 0.000 claims description 7
• 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 7
• 201000010374 Down Syndrome Diseases 0.000 claims description 7
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 7
• 208000012902 Nervous system disease Diseases 0.000 claims description 7
• 208000025966 Neurological disease Diseases 0.000 claims description 7
• 208000018737 Parkinson disease Diseases 0.000 claims description 7
• 238000006243 chemical reaction Methods 0.000 claims description 7
• 239000003795 chemical substances by application Substances 0.000 claims description 7
• 201000006417 multiple sclerosis Diseases 0.000 claims description 7
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 7
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 7
• LZXHHNKULPHARO-UHFFFAOYSA-M (3,4-dichlorophenyl)methyl-triphenylphosphanium;chloride Chemical compound [Cl-].C1=C(Cl)C(Cl)=CC=C1C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 LZXHHNKULPHARO-UHFFFAOYSA-M 0.000 claims description 6
• SNKZJIOFVMKAOJ-UHFFFAOYSA-N 3-Amino-1-propanesulfonic acid Natural products NCCCS(O)(=O)=O SNKZJIOFVMKAOJ-UHFFFAOYSA-N 0.000 claims description 6
• 206010007509 Cardiac amyloidosis Diseases 0.000 claims description 6
• 239000003112 inhibitor Substances 0.000 claims description 6
• 238000012544 monitoring process Methods 0.000 claims description 6
• 238000002360 preparation method Methods 0.000 claims description 6
• 229960001685 tacrine Drugs 0.000 claims description 6
• YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 claims description 6
• 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 claims description 5
• 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 claims description 5
• 206010014714 Endocrine neoplasms Diseases 0.000 claims description 5
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 5
• 239000002738 chelating agent Substances 0.000 claims description 5
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 5
• 235000018417 cysteine Nutrition 0.000 claims description 5
• 229960003530 donepezil Drugs 0.000 claims description 5
• 229960003980 galantamine Drugs 0.000 claims description 5
• ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 claims description 5
• 229910052751 metal Inorganic materials 0.000 claims description 5
• 239000002184 metal Substances 0.000 claims description 5
• 239000002858 neurotransmitter agent Substances 0.000 claims description 5
• 235000015872 dietary supplement Nutrition 0.000 claims description 4
• 230000033616 DNA repair Effects 0.000 claims description 3
• XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 claims description 3
• 206010044688 Trisomy 21 Diseases 0.000 claims description 3
• 239000012190 activator Substances 0.000 claims description 3
• 230000002424 anti-apoptotic effect Effects 0.000 claims description 3
• 230000003110 anti-inflammatory effect Effects 0.000 claims description 3
• 239000002439 beta secretase inhibitor Substances 0.000 claims description 3
• 238000012258 culturing Methods 0.000 claims description 3
• 239000003540 gamma secretase inhibitor Substances 0.000 claims description 3
• 239000002207 metabolite Substances 0.000 claims description 3
• RMHMFHUVIITRHF-UHFFFAOYSA-N pirenzepine Chemical compound C1CN(C)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC=CC=C21 RMHMFHUVIITRHF-UHFFFAOYSA-N 0.000 claims description 3
• 229960004633 pirenzepine Drugs 0.000 claims description 3
• MGNVWUDMMXZUDI-UHFFFAOYSA-N propane-1,3-disulfonic acid Chemical compound OS(=O)(=O)CCCS(O)(=O)=O MGNVWUDMMXZUDI-UHFFFAOYSA-N 0.000 claims description 3
• 230000009467 reduction Effects 0.000 claims description 3
• 230000004043 responsiveness Effects 0.000 claims description 3
• 102000013498 tau Proteins Human genes 0.000 claims description 3
• 108010026424 tau Proteins Proteins 0.000 claims description 3
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 claims description 2
• 102000017727 Immunoglobulin Variable Region Human genes 0.000 claims description 2
• 230000015556 catabolic process Effects 0.000 claims description 2
• 238000006731 degradation reaction Methods 0.000 claims description 2
• 230000036542 oxidative stress Effects 0.000 claims description 2
• 229960004136 rivastigmine Drugs 0.000 claims description 2
• 229940125373 Gamma-Secretase Inhibitor Drugs 0.000 claims 1
• 208000019802 Sexually transmitted disease Diseases 0.000 claims 1
• 208000037765 diseases and disorders Diseases 0.000 claims 1
• 238000013467 fragmentation Methods 0.000 claims 1
• 238000006062 fragmentation reaction Methods 0.000 claims 1
• 235000004400 serine Nutrition 0.000 claims 1
• 150000003355 serines Chemical class 0.000 claims 1
• 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 139
• 239000000178 monomer Substances 0.000 description 125
• 239000000835 fiber Substances 0.000 description 68
• 241001465754 Metazoa Species 0.000 description 61
• JADVWWSKYZXRGX-UHFFFAOYSA-M thioflavine T Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1C1=[N+](C)C2=CC=C(C)C=C2S1 JADVWWSKYZXRGX-UHFFFAOYSA-M 0.000 description 59
• 230000004927 fusion Effects 0.000 description 52
• 239000002953 phosphate buffered saline Substances 0.000 description 51
• 230000002776 aggregation Effects 0.000 description 50
• 238000004220 aggregation Methods 0.000 description 50
• 239000000523 sample Substances 0.000 description 47
• 239000000243 solution Substances 0.000 description 46
• 229940024606 amino acid Drugs 0.000 description 45
• 238000002965 ELISA Methods 0.000 description 40
• 229960002685 biotin Drugs 0.000 description 37
• 239000011616 biotin Substances 0.000 description 37
• 238000003271 compound fluorescence assay Methods 0.000 description 35
• 230000005764 inhibitory process Effects 0.000 description 35
• 241000699666 Mus <mouse, genus> Species 0.000 description 32
• 238000009472 formulation Methods 0.000 description 32
• 241000124008 Mammalia Species 0.000 description 31
• 229920001223 polyethylene glycol Polymers 0.000 description 31
• 206010028980 Neoplasm Diseases 0.000 description 30
• 239000002202 Polyethylene glycol Substances 0.000 description 30
• 238000002474 experimental method Methods 0.000 description 28
• 239000007924 injection Substances 0.000 description 27
• 238000002347 injection Methods 0.000 description 27
• 239000002502 liposome Substances 0.000 description 27
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 26
• 241000699660 Mus musculus Species 0.000 description 26
• 238000003556 assay Methods 0.000 description 25
• IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 25
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
• 230000001747 exhibiting effect Effects 0.000 description 24
• 239000000872 buffer Substances 0.000 description 22
• 230000002209 hydrophobic effect Effects 0.000 description 21
• 238000010790 dilution Methods 0.000 description 19
• 239000012895 dilution Substances 0.000 description 19
• 206010064930 age-related macular degeneration Diseases 0.000 description 18
• 238000004458 analytical method Methods 0.000 description 18
• 238000012286 ELISA Assay Methods 0.000 description 17
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 16
• 241000282412 Homo Species 0.000 description 16
• 108010033276 Peptide Fragments Proteins 0.000 description 16
• 102000007079 Peptide Fragments Human genes 0.000 description 16
• 125000000539 amino acid group Chemical group 0.000 description 16
• 230000003053 immunization Effects 0.000 description 16
• 230000002401 inhibitory effect Effects 0.000 description 16
• 150000003904 phospholipids Chemical class 0.000 description 16
• 239000000047 product Substances 0.000 description 16
• 238000003786 synthesis reaction Methods 0.000 description 16
• 208000037259 Amyloid Plaque Diseases 0.000 description 15
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
• 239000002671 adjuvant Substances 0.000 description 15
• 229940098773 bovine serum albumin Drugs 0.000 description 15
• 239000000126 substance Substances 0.000 description 15
• 208000024891 symptom Diseases 0.000 description 15
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 14
• 238000001542 size-exclusion chromatography Methods 0.000 description 14
• 210000004881 tumor cell Anatomy 0.000 description 14
• 102000001049 Amyloid Human genes 0.000 description 13
• 108010094108 Amyloid Proteins 0.000 description 13
• 102000009091 Amyloidogenic Proteins Human genes 0.000 description 13
• 108010048112 Amyloidogenic Proteins Proteins 0.000 description 13
• 241000699670 Mus sp. Species 0.000 description 13
• 239000002253 acid Substances 0.000 description 13
• DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 13
• 235000020958 biotin Nutrition 0.000 description 13
• 230000008499 blood brain barrier function Effects 0.000 description 13
• 210000001218 blood-brain barrier Anatomy 0.000 description 13
• 238000005859 coupling reaction Methods 0.000 description 13
• 238000001514 detection method Methods 0.000 description 13
• 229940079593 drug Drugs 0.000 description 13
• 238000002649 immunization Methods 0.000 description 13
• 108010038807 Oligopeptides Proteins 0.000 description 12
• 102000015636 Oligopeptides Human genes 0.000 description 12
• 235000021314 Palmitic acid Nutrition 0.000 description 12
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 12
• 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 12
• 230000028993 immune response Effects 0.000 description 12
• 238000011534 incubation Methods 0.000 description 12
• WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 12
• -1 resamine Chemical compound 0.000 description 12
• 239000011347 resin Substances 0.000 description 12
• 229920005989 resin Polymers 0.000 description 12
• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 11
• 108010064397 amyloid beta-protein (1-40) Proteins 0.000 description 11
• 238000010168 coupling process Methods 0.000 description 11
• 238000001727 in vivo Methods 0.000 description 11
• 230000003993 interaction Effects 0.000 description 11
• 238000004519 manufacturing process Methods 0.000 description 11
• 239000011159 matrix material Substances 0.000 description 11
• 238000005406 washing Methods 0.000 description 11
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 10
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 10
• 108060003951 Immunoglobulin Proteins 0.000 description 10
• 238000005481 NMR spectroscopy Methods 0.000 description 10
• 230000008878 coupling Effects 0.000 description 10
• 230000009977 dual effect Effects 0.000 description 10
• 230000006870 function Effects 0.000 description 10
• 238000009396 hybridization Methods 0.000 description 10
• 102000018358 immunoglobulin Human genes 0.000 description 10
• 150000002632 lipids Chemical class 0.000 description 10
• 230000001404 mediated effect Effects 0.000 description 10
• 239000012071 phase Substances 0.000 description 10
• 210000002966 serum Anatomy 0.000 description 10
• 210000001519 tissue Anatomy 0.000 description 10
• 229960005486 vaccine Drugs 0.000 description 10
• 108010060159 Apolipoprotein E4 Proteins 0.000 description 9
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 9
• 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 9
• 108010067902 Peptide Library Proteins 0.000 description 9
• 230000008859 change Effects 0.000 description 9
• 238000011065 in-situ storage Methods 0.000 description 9
• 239000012528 membrane Substances 0.000 description 9
• NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 8
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
• 208000001976 Endocrine Gland Neoplasms Diseases 0.000 description 8
• 206010035226 Plasma cell myeloma Diseases 0.000 description 8
• 102000054727 Serum Amyloid A Human genes 0.000 description 8
• 108700028909 Serum Amyloid A Proteins 0.000 description 8
• COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 8
• 201000011523 endocrine gland cancer Diseases 0.000 description 8
• 230000004438 eyesight Effects 0.000 description 8
• 239000008194 pharmaceutical composition Substances 0.000 description 8
• 238000006116 polymerization reaction Methods 0.000 description 8
• 238000013207 serial dilution Methods 0.000 description 8
• 230000009261 transgenic effect Effects 0.000 description 8
• XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 7
• 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 7
• 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 7
• 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 7
• 108020004414 DNA Proteins 0.000 description 7
• 102000004190 Enzymes Human genes 0.000 description 7
• 108090000790 Enzymes Proteins 0.000 description 7
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 7
• 206010025421 Macule Diseases 0.000 description 7
• 229920001213 Polysorbate 20 Polymers 0.000 description 7
• 208000000208 Wet Macular Degeneration Diseases 0.000 description 7
• 210000000746 body region Anatomy 0.000 description 7
• 229940088598 enzyme Drugs 0.000 description 7
• 238000011156 evaluation Methods 0.000 description 7
• 230000001900 immune effect Effects 0.000 description 7
• 238000003018 immunoassay Methods 0.000 description 7
• 230000005847 immunogenicity Effects 0.000 description 7
• GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 7
• 230000007246 mechanism Effects 0.000 description 7
• 210000004379 membrane Anatomy 0.000 description 7
• 230000004048 modification Effects 0.000 description 7
• 238000012986 modification Methods 0.000 description 7
• 229940126619 mouse monoclonal antibody Drugs 0.000 description 7
• 201000000050 myeloid neoplasm Diseases 0.000 description 7
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 7
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 7
• 239000013641 positive control Substances 0.000 description 7
• 239000000843 powder Substances 0.000 description 7
• 230000002829 reductive effect Effects 0.000 description 7
• 238000000926 separation method Methods 0.000 description 7
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 7
• 238000010186 staining Methods 0.000 description 7
• 238000004627 transmission electron microscopy Methods 0.000 description 7
• 235000012431 wafers Nutrition 0.000 description 7
• 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 6
• 208000023769 AA amyloidosis Diseases 0.000 description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• 201000004569 Blindness Diseases 0.000 description 6
• 108091026890 Coding region Proteins 0.000 description 6
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
• 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 6
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 6
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
• 206010039811 Secondary amyloidosis Diseases 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 108010090804 Streptavidin Proteins 0.000 description 6
• IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 6
• 239000012491 analyte Substances 0.000 description 6
• 238000004873 anchoring Methods 0.000 description 6
• 210000004204 blood vessel Anatomy 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 235000012000 cholesterol Nutrition 0.000 description 6
• 238000002298 density-gradient ultracentrifugation Methods 0.000 description 6
• 238000010511 deprotection reaction Methods 0.000 description 6
• 238000003745 diagnosis Methods 0.000 description 6
• PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 6
• FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 6
• 125000005647 linker group Chemical group 0.000 description 6
• 239000006166 lysate Substances 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 230000003287 optical effect Effects 0.000 description 6
• 229920000747 poly(lactic acid) Polymers 0.000 description 6
• 230000008569 process Effects 0.000 description 6
• 125000006239 protecting group Chemical group 0.000 description 6
• 238000011002 quantification Methods 0.000 description 6
• 239000007787 solid Substances 0.000 description 6
• 210000004989 spleen cell Anatomy 0.000 description 6
• 238000009007 Diagnostic Kit Methods 0.000 description 5
• 241000283973 Oryctolagus cuniculus Species 0.000 description 5
• 230000002159 abnormal effect Effects 0.000 description 5
• 230000035508 accumulation Effects 0.000 description 5
• 238000009825 accumulation Methods 0.000 description 5
• 239000013543 active substance Substances 0.000 description 5
• 150000001412 amines Chemical class 0.000 description 5
• 125000004432 carbon atom Chemical group C* 0.000 description 5
• 229960001231 choline Drugs 0.000 description 5
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 5
• 238000003776 cleavage reaction Methods 0.000 description 5
• 235000014113 dietary fatty acids Nutrition 0.000 description 5
• 239000000194 fatty acid Substances 0.000 description 5
• 229930195729 fatty acid Natural products 0.000 description 5
• 150000004665 fatty acids Chemical group 0.000 description 5
• 210000004754 hybrid cell Anatomy 0.000 description 5
• 238000000338 in vitro Methods 0.000 description 5
• 238000001990 intravenous administration Methods 0.000 description 5
• 230000004807 localization Effects 0.000 description 5
• 229920000642 polymer Polymers 0.000 description 5
• 238000011160 research Methods 0.000 description 5
• 230000007017 scission Effects 0.000 description 5
• 230000009870 specific binding Effects 0.000 description 5
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
• 101800001718 Amyloid-beta protein Proteins 0.000 description 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• 238000011740 C57BL/6 mouse Methods 0.000 description 4
• 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 4
• 229920002307 Dextran Polymers 0.000 description 4
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 4
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
• 241001494479 Pecora Species 0.000 description 4
• 229920000954 Polyglycolide Polymers 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• 238000007792 addition Methods 0.000 description 4
• 230000004931 aggregating effect Effects 0.000 description 4
• 229910021529 ammonia Inorganic materials 0.000 description 4
• 230000006933 amyloid-beta aggregation Effects 0.000 description 4
• 230000003942 amyloidogenic effect Effects 0.000 description 4
• 239000012736 aqueous medium Substances 0.000 description 4
• 210000003719 b-lymphocyte Anatomy 0.000 description 4
• 239000011324 bead Substances 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 210000004369 blood Anatomy 0.000 description 4
• 239000008280 blood Substances 0.000 description 4
• 229910052799 carbon Inorganic materials 0.000 description 4
• 230000007910 cell fusion Effects 0.000 description 4
• 210000001175 cerebrospinal fluid Anatomy 0.000 description 4
• 230000001684 chronic effect Effects 0.000 description 4
• 239000011248 coating agent Substances 0.000 description 4
• 238000000576 coating method Methods 0.000 description 4
• 230000009260 cross reactivity Effects 0.000 description 4
• 230000008021 deposition Effects 0.000 description 4
• 229960002086 dextran Drugs 0.000 description 4
• UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 4
• VWLWTJHKQHRTNC-UHFFFAOYSA-L dipotassium;8-anilino-5-(4-anilino-5-sulfonatonaphthalen-1-yl)naphthalene-1-sulfonate Chemical compound [K+].[K+].C=12C(S(=O)(=O)[O-])=CC=CC2=C(C=2C3=CC=CC(=C3C(NC=3C=CC=CC=3)=CC=2)S([O-])(=O)=O)C=CC=1NC1=CC=CC=C1 VWLWTJHKQHRTNC-UHFFFAOYSA-L 0.000 description 4
• 208000011325 dry age related macular degeneration Diseases 0.000 description 4
• 239000000839 emulsion Substances 0.000 description 4
• 150000004676 glycans Chemical class 0.000 description 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 4
• 238000002173 high-resolution transmission electron microscopy Methods 0.000 description 4
• 230000002163 immunogen Effects 0.000 description 4
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
• 238000013507 mapping Methods 0.000 description 4
• 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 4
• 238000005259 measurement Methods 0.000 description 4
• 239000002245 particle Substances 0.000 description 4
• 210000002381 plasma Anatomy 0.000 description 4
• 230000003389 potentiating effect Effects 0.000 description 4
• 210000004129 prosencephalon Anatomy 0.000 description 4
• 238000000159 protein binding assay Methods 0.000 description 4
• 238000004062 sedimentation Methods 0.000 description 4
• 238000010996 solid-state NMR spectroscopy Methods 0.000 description 4
• 238000000371 solid-state nuclear magnetic resonance spectroscopy Methods 0.000 description 4
• 230000003595 spectral effect Effects 0.000 description 4
• 238000013268 sustained release Methods 0.000 description 4
• 239000012730 sustained-release form Substances 0.000 description 4
• 230000007704 transition Effects 0.000 description 4
• 238000002255 vaccination Methods 0.000 description 4
• 230000004393 visual impairment Effects 0.000 description 4
• 230000003442 weekly effect Effects 0.000 description 4
• YPTNAIDIXCOZAJ-LHEWISCISA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-6-[[(4-methylphenyl)-diphenylmethyl]amino]hexanoic acid Chemical compound C1=CC(C)=CC=C1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)NCCCC[C@@H](C(O)=O)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 YPTNAIDIXCOZAJ-LHEWISCISA-N 0.000 description 3
• CIEMDIKTFOLQML-UHFFFAOYSA-N 2-amino-1-sulfanylethanol Chemical compound NCC(O)S CIEMDIKTFOLQML-UHFFFAOYSA-N 0.000 description 3
• TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• 108010025628 Apolipoproteins E Proteins 0.000 description 3
• 102000013918 Apolipoproteins E Human genes 0.000 description 3
• DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 3
• 108010078791 Carrier Proteins Proteins 0.000 description 3
• 208000028698 Cognitive impairment Diseases 0.000 description 3
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
• 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 3
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
• UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 3
• 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 3
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
• 239000000020 Nitrocellulose Substances 0.000 description 3
• 241000276498 Pollachius virens Species 0.000 description 3
• 239000004793 Polystyrene Substances 0.000 description 3
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 241000700159 Rattus Species 0.000 description 3
• 239000003875 Wang resin Substances 0.000 description 3
• NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 3
• 229960003896 aminopterin Drugs 0.000 description 3
• 239000003963 antioxidant agent Substances 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• 230000003542 behavioural effect Effects 0.000 description 3
• IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 3
• 239000012472 biological sample Substances 0.000 description 3
• 230000005540 biological transmission Effects 0.000 description 3
• 210000004899 c-terminal region Anatomy 0.000 description 3
• 230000003930 cognitive ability Effects 0.000 description 3
• 229920001577 copolymer Polymers 0.000 description 3
• 230000006378 damage Effects 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• 239000008121 dextrose Substances 0.000 description 3
• KAKKHKRHCKCAGH-UHFFFAOYSA-L disodium;(4-nitrophenyl) phosphate;hexahydrate Chemical compound O.O.O.O.O.O.[Na+].[Na+].[O-][N+](=O)C1=CC=C(OP([O-])([O-])=O)C=C1 KAKKHKRHCKCAGH-UHFFFAOYSA-L 0.000 description 3
• 238000004401 flow injection analysis Methods 0.000 description 3
• 239000012530 fluid Substances 0.000 description 3
• 208000035474 group of disease Diseases 0.000 description 3
• 230000012010 growth Effects 0.000 description 3
• 230000036541 health Effects 0.000 description 3
• 230000000977 initiatory effect Effects 0.000 description 3
• 238000003780 insertion Methods 0.000 description 3
• 230000037431 insertion Effects 0.000 description 3
• 238000007912 intraperitoneal administration Methods 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• 230000000670 limiting effect Effects 0.000 description 3
• 239000002609 medium Substances 0.000 description 3
• BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 3
• 208000015122 neurodegenerative disease Diseases 0.000 description 3
• 210000002569 neuron Anatomy 0.000 description 3
• 229920001220 nitrocellulos Polymers 0.000 description 3
• 238000006384 oligomerization reaction Methods 0.000 description 3
• 230000006320 pegylation Effects 0.000 description 3
• 238000010647 peptide synthesis reaction Methods 0.000 description 3
• 230000007505 plaque formation Effects 0.000 description 3
• 229920001282 polysaccharide Polymers 0.000 description 3
• 239000005017 polysaccharide Substances 0.000 description 3
• 229920002223 polystyrene Polymers 0.000 description 3
• 230000000644 propagated effect Effects 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 210000001525 retina Anatomy 0.000 description 3
• 230000035945 sensitivity Effects 0.000 description 3
• 241000894007 species Species 0.000 description 3
• 238000010561 standard procedure Methods 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• 208000011580 syndromic disease Diseases 0.000 description 3
• 229940104230 thymidine Drugs 0.000 description 3
• 238000011830 transgenic mouse model Methods 0.000 description 3
• OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 2
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
• LVNGJLRDBYCPGB-LDLOPFEMSA-N (R)-1,2-distearoylphosphatidylethanolamine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-LDLOPFEMSA-N 0.000 description 2
• JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 2
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
• WLCZTRVUXYALDD-IBGZPJMESA-N 7-[[(2s)-2,6-bis(2-methoxyethoxycarbonylamino)hexanoyl]amino]heptoxy-methylphosphinic acid Chemical compound COCCOC(=O)NCCCC[C@H](NC(=O)OCCOC)C(=O)NCCCCCCCOP(C)(O)=O WLCZTRVUXYALDD-IBGZPJMESA-N 0.000 description 2
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
• 206010002942 Apathy Diseases 0.000 description 2
• 208000002109 Argyria Diseases 0.000 description 2
• CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 description 2
• 240000002900 Arthrospira platensis Species 0.000 description 2
• 235000016425 Arthrospira platensis Nutrition 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 241000894006 Bacteria Species 0.000 description 2
• 241000208199 Buxus sempervirens Species 0.000 description 2
• 241000283707 Capra Species 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• 102000014914 Carrier Proteins Human genes 0.000 description 2
• 108091006146 Channels Proteins 0.000 description 2
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
• 206010061818 Disease progression Diseases 0.000 description 2
• 238000008157 ELISA kit Methods 0.000 description 2
• 201000011240 Frontotemporal dementia Diseases 0.000 description 2
• 102000003886 Glycoproteins Human genes 0.000 description 2
• 108090000288 Glycoproteins Proteins 0.000 description 2
• 229920002683 Glycosaminoglycan Polymers 0.000 description 2
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
• 239000004472 Lysine Substances 0.000 description 2
• XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
• 208000026139 Memory disease Diseases 0.000 description 2
• 241001529936 Murinae Species 0.000 description 2
• 108091028043 Nucleic acid sequence Proteins 0.000 description 2
• 239000005642 Oleic acid Substances 0.000 description 2
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
• 206010031252 Osteomyelitis Diseases 0.000 description 2
• 229930040373 Paraformaldehyde Natural products 0.000 description 2
• 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 2
• 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 2
• 239000004743 Polypropylene Substances 0.000 description 2
• 102000015499 Presenilins Human genes 0.000 description 2
• 108010050254 Presenilins Proteins 0.000 description 2
• 108010071390 Serum Albumin Proteins 0.000 description 2
• 102000007562 Serum Albumin Human genes 0.000 description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• 239000012505 Superdex™ Substances 0.000 description 2
• 210000001744 T-lymphocyte Anatomy 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• 108090000848 Ubiquitin Proteins 0.000 description 2
• 102000044159 Ubiquitin Human genes 0.000 description 2
• 238000002835 absorbance Methods 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 239000003242 anti bacterial agent Substances 0.000 description 2
• 210000000628 antibody-producing cell Anatomy 0.000 description 2
• 239000003125 aqueous solvent Substances 0.000 description 2
• 229910052786 argon Inorganic materials 0.000 description 2
• 229960004372 aripiprazole Drugs 0.000 description 2
• 230000004888 barrier function Effects 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
• 238000012742 biochemical analysis Methods 0.000 description 2
• 230000000903 blocking effect Effects 0.000 description 2
• 210000001124 body fluid Anatomy 0.000 description 2
• 239000010839 body fluid Substances 0.000 description 2
• 210000001775 bruch membrane Anatomy 0.000 description 2
• 239000007853 buffer solution Substances 0.000 description 2
• 210000002318 cardia Anatomy 0.000 description 2
• 238000005277 cation exchange chromatography Methods 0.000 description 2
• 230000002490 cerebral effect Effects 0.000 description 2
• 238000012512 characterization method Methods 0.000 description 2
• 229960004170 clozapine Drugs 0.000 description 2
• QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 2
• 230000019771 cognition Effects 0.000 description 2
• 230000003920 cognitive function Effects 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
• 230000007850 degeneration Effects 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 230000005750 disease progression Effects 0.000 description 2
• 208000035475 disorder Diseases 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 238000004090 dissolution Methods 0.000 description 2
• 238000009826 distribution Methods 0.000 description 2
• POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
• 239000000975 dye Substances 0.000 description 2
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
• 239000002158 endotoxin Substances 0.000 description 2
• 210000001353 entorhinal cortex Anatomy 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• 208000030533 eye disease Diseases 0.000 description 2
• 238000007667 floating Methods 0.000 description 2
• 108020001507 fusion proteins Proteins 0.000 description 2
• 102000037865 fusion proteins Human genes 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 238000001415 gene therapy Methods 0.000 description 2
• 230000002068 genetic effect Effects 0.000 description 2
• 239000004220 glutamic acid Substances 0.000 description 2
• 235000013922 glutamic acid Nutrition 0.000 description 2
• 238000003306 harvesting Methods 0.000 description 2
• 210000002865 immune cell Anatomy 0.000 description 2
• 229940127121 immunoconjugate Drugs 0.000 description 2
• 230000016784 immunoglobulin production Effects 0.000 description 2
• 239000002955 immunomodulating agent Substances 0.000 description 2
• 229940121354 immunomodulator Drugs 0.000 description 2
• 230000001771 impaired effect Effects 0.000 description 2
• 230000010354 integration Effects 0.000 description 2
• 238000001361 intraarterial administration Methods 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 239000007928 intraperitoneal injection Substances 0.000 description 2
• NBQNWMBBSKPBAY-UHFFFAOYSA-N iodixanol Chemical compound IC=1C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C(I)C=1N(C(=O)C)CC(O)CN(C(C)=O)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NBQNWMBBSKPBAY-UHFFFAOYSA-N 0.000 description 2
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
• 238000012933 kinetic analysis Methods 0.000 description 2
• 239000004310 lactic acid Substances 0.000 description 2
• 235000014655 lactic acid Nutrition 0.000 description 2
• 229920006008 lipopolysaccharide Polymers 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 208000018769 loss of vision Diseases 0.000 description 2
• 231100000864 loss of vision Toxicity 0.000 description 2
• 230000002934 lysing effect Effects 0.000 description 2
• 238000004949 mass spectrometry Methods 0.000 description 2
• 230000008774 maternal effect Effects 0.000 description 2
• 229960004640 memantine Drugs 0.000 description 2
• 230000003340 mental effect Effects 0.000 description 2
• 235000013336 milk Nutrition 0.000 description 2
• 239000008267 milk Substances 0.000 description 2
• 210000004080 milk Anatomy 0.000 description 2
• 230000009149 molecular binding Effects 0.000 description 2
• 210000002161 motor neuron Anatomy 0.000 description 2
• 230000000926 neurological effect Effects 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical group CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Chemical group CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
• 229960005017 olanzapine Drugs 0.000 description 2
• KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 2
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
• 235000021313 oleic acid Nutrition 0.000 description 2
• 239000006186 oral dosage form Substances 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• 230000008506 pathogenesis Effects 0.000 description 2
• 230000035699 permeability Effects 0.000 description 2
• 150000002978 peroxides Chemical class 0.000 description 2
• 239000003016 pheromone Substances 0.000 description 2
• 238000005375 photometry Methods 0.000 description 2
• 238000000053 physical method Methods 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• 229920001308 poly(aminoacid) Polymers 0.000 description 2
• 239000004626 polylactic acid Substances 0.000 description 2
• 229920006324 polyoxymethylene Polymers 0.000 description 2
• 229920001155 polypropylene Polymers 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 230000001681 protective effect Effects 0.000 description 2
• 230000005180 public health Effects 0.000 description 2
• 230000002285 radioactive effect Effects 0.000 description 2
• 230000009257 reactivity Effects 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 230000008929 regeneration Effects 0.000 description 2
• 238000011069 regeneration method Methods 0.000 description 2
• 210000003583 retinal pigment epithelium Anatomy 0.000 description 2
• 210000001202 rhombencephalon Anatomy 0.000 description 2
• 229960001534 risperidone Drugs 0.000 description 2
• RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 2
• 239000012723 sample buffer Substances 0.000 description 2
• 210000003625 skull Anatomy 0.000 description 2
• 239000001632 sodium acetate Substances 0.000 description 2
• 235000017281 sodium acetate Nutrition 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 239000007790 solid phase Substances 0.000 description 2
• 239000012453 solvate Substances 0.000 description 2
• 239000002904 solvent Substances 0.000 description 2
• 125000006850 spacer group Chemical group 0.000 description 2
• 238000001228 spectrum Methods 0.000 description 2
• 229940082787 spirulina Drugs 0.000 description 2
• 210000000952 spleen Anatomy 0.000 description 2
• 239000008117 stearic acid Chemical group 0.000 description 2
• 238000005728 strengthening Methods 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 230000002194 synthesizing effect Effects 0.000 description 2
• TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical group CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 238000005199 ultracentrifugation Methods 0.000 description 2
• 239000003981 vehicle Substances 0.000 description 2
• 229960000607 ziprasidone Drugs 0.000 description 2
• MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 description 2
• KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
• OLDGKSQBWGEFNM-FQEVSTJZSA-N (2s)-6-amino-2-(hexadecanoylamino)hexanoic acid Chemical compound CCCCCCCCCCCCCCCC(=O)N[C@H](C(O)=O)CCCCN OLDGKSQBWGEFNM-FQEVSTJZSA-N 0.000 description 1
• XOYXESIZZFUVRD-UVSAJTFZSA-N (2s,3s,4r,5s,6s)-6-[(2r,3r,4r,5s,6r)-6-[(2r,3s,4r,5s,6r)-5-acetamido-6-[(2r,3r,4r,5s,6r)-4-acetyloxy-6-[(2r,3r,4r,5s,6r)-4-acetyloxy-6-[(2r,3r,4r,5s,6s)-4-acetyloxy-5-hydroxy-2-(hydroxymethyl)-6-methoxyoxan-3-yl]oxy-5-hydroxy-2-(hydroxymethyl)oxan-3-yl]ox Chemical compound CC(=O)O[C@@H]1[C@H](O)[C@@H](OC)O[C@H](CO)[C@H]1O[C@@H]1[C@@H](O)[C@@H](OC(C)=O)[C@H](O[C@@H]2[C@H]([C@@H](OC(C)=O)[C@H](O[C@@H]3[C@H]([C@@H](O)[C@H](O[C@@H]4[C@H]([C@@H](OC(C)=O)[C@H](O[C@@H]5[C@H]([C@@H](OC(C)=O)[C@H](O[C@@H]6[C@H]([C@@H](OC(C)=O)[C@H](O[C@@H]7[C@H]([C@@H](OC(C)=O)[C@H](OC)[C@@H](CO)O7)O)[C@@H](CO)O6)O)[C@H](O5)C(O)=O)O)[C@@H](CO)O4)O)[C@@H](CO)O3)NC(C)=O)[C@@H](CO)O2)O)[C@@H](CO)O1 XOYXESIZZFUVRD-UVSAJTFZSA-N 0.000 description 1
• LTAIJLDCJFZBKT-SECBINFHSA-N (3R)-3-hydroxy-3-[(trimethylazaniumyl)methyl]pentanoate Chemical compound C(C)[C@](O)(C[N+](C)(C)C)CC([O-])=O LTAIJLDCJFZBKT-SECBINFHSA-N 0.000 description 1
• CITHEXJVPOWHKC-UUWRZZSWSA-N 1,2-di-O-myristoyl-sn-glycero-3-phosphocholine Chemical group CCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCC CITHEXJVPOWHKC-UUWRZZSWSA-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
• NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-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
• QWVRTSZDKPRPDF-UHFFFAOYSA-N 5-(piperidin-1-ylmethyl)-3-pyridin-3-yl-5,6-dihydro-2h-1,2,4-oxadiazine Chemical compound C1CCCCN1CC(N=1)CONC=1C1=CC=CN=C1 QWVRTSZDKPRPDF-UHFFFAOYSA-N 0.000 description 1
• SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
• LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 1
• 208000023761 AL amyloidosis Diseases 0.000 description 1
• 102000011767 Acute-Phase Proteins Human genes 0.000 description 1
• 108010062271 Acute-Phase Proteins Proteins 0.000 description 1
• 108700028369 Alleles Proteins 0.000 description 1
• 102100026882 Alpha-synuclein Human genes 0.000 description 1
• 102000018430 Amyloid-beta precursor proteins Human genes 0.000 description 1
• 108050007552 Amyloid-beta precursor proteins Proteins 0.000 description 1
• 108090000668 Annexin A2 Proteins 0.000 description 1
• 102100034613 Annexin A2 Human genes 0.000 description 1
• 208000019901 Anxiety disease Diseases 0.000 description 1
• 102100029470 Apolipoprotein E Human genes 0.000 description 1
• 101710095339 Apolipoprotein E Proteins 0.000 description 1
• 241000271566 Aves Species 0.000 description 1
• 208000035143 Bacterial infection Diseases 0.000 description 1
• 102100026189 Beta-galactosidase Human genes 0.000 description 1
• 241000588832 Bordetella pertussis Species 0.000 description 1
• 102400000967 Bradykinin Human genes 0.000 description 1
• 101800004538 Bradykinin Proteins 0.000 description 1
• DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
• 208000002177 Cataract Diseases 0.000 description 1
• 241001227713 Chiron Species 0.000 description 1
• 229920002101 Chitin Polymers 0.000 description 1
• 229940122041 Cholinesterase inhibitor Drugs 0.000 description 1
• 102000003914 Cholinesterases Human genes 0.000 description 1
• 108090000322 Cholinesterases Proteins 0.000 description 1
• 229920001287 Chondroitin sulfate Polymers 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
• IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
• 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 1
• CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
• 206010012239 Delusion Diseases 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 206010016202 Familial Amyloidosis Diseases 0.000 description 1
• 206010016207 Familial Mediterranean fever Diseases 0.000 description 1
• BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
• 108010040721 Flagellin Proteins 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
• 241000237858 Gastropoda Species 0.000 description 1
• 208000008069 Geographic Atrophy Diseases 0.000 description 1
• 244000194101 Ginkgo biloba Species 0.000 description 1
• 235000008100 Ginkgo biloba Nutrition 0.000 description 1
• SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
• 102000005720 Glutathione transferase Human genes 0.000 description 1
• 108010070675 Glutathione transferase Proteins 0.000 description 1
• 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 1
• 208000004547 Hallucinations Diseases 0.000 description 1
• 208000032843 Hemorrhage Diseases 0.000 description 1
• 206010019851 Hepatotoxicity Diseases 0.000 description 1
• 241000238631 Hexapoda Species 0.000 description 1
• 208000017604 Hodgkin disease Diseases 0.000 description 1
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
• 208000005531 Immunoglobulin Light-chain Amyloidosis Diseases 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 102000000589 Interleukin-1 Human genes 0.000 description 1
• 108010002352 Interleukin-1 Proteins 0.000 description 1
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
• 102000007330 LDL Lipoproteins Human genes 0.000 description 1
• 108010007622 LDL Lipoproteins Proteins 0.000 description 1
• 239000005639 Lauric acid Substances 0.000 description 1
• 206010024229 Leprosy Diseases 0.000 description 1
• 101710105045 Lipoprotein E Proteins 0.000 description 1
• 102000004895 Lipoproteins Human genes 0.000 description 1
• 108090001030 Lipoproteins Proteins 0.000 description 1
• 208000010415 Low Vision Diseases 0.000 description 1
• DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
• 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 1
• 229920000057 Mannan Polymers 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 206010063341 Metamorphopsia Diseases 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• 206010028289 Muscle atrophy Diseases 0.000 description 1
• 208000029578 Muscle disease Diseases 0.000 description 1
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
• 229940127523 NMDA Receptor Antagonists Drugs 0.000 description 1
• OLDGKSQBWGEFNM-UHFFFAOYSA-N Nalpha -palmitoyl-lysine Natural products CCCCCCCCCCCCCCCC(=O)NC(C(O)=O)CCCCN OLDGKSQBWGEFNM-UHFFFAOYSA-N 0.000 description 1
• 206010029240 Neuritis Diseases 0.000 description 1
• 102000008763 Neurofilament Proteins Human genes 0.000 description 1
• 108010088373 Neurofilament Proteins Proteins 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• 239000004677 Nylon Substances 0.000 description 1
• FOKFIEDUDVADAO-UHFFFAOYSA-L O.O.O.O.O.O.P(=O)([O-])([O-])O.[Na+].[Na+].P(=O)(OC1=CC=C(C=C1)[N+](=O)[O-])(O)O Chemical compound O.O.O.O.O.O.P(=O)([O-])([O-])O.[Na+].[Na+].P(=O)(OC1=CC=C(C=C1)[N+](=O)[O-])(O)O FOKFIEDUDVADAO-UHFFFAOYSA-L 0.000 description 1
• 206010061323 Optic neuropathy Diseases 0.000 description 1
• 108010058846 Ovalbumin Proteins 0.000 description 1
• 229920002230 Pectic acid Polymers 0.000 description 1
• 108090000284 Pepsin A Proteins 0.000 description 1
• 102000057297 Pepsin A Human genes 0.000 description 1
• 208000037581 Persistent Infection Diseases 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 229920002732 Polyanhydride Polymers 0.000 description 1
• 102000004257 Potassium Channel Human genes 0.000 description 1
• 206010036673 Primary amyloidosis Diseases 0.000 description 1
• 206010036790 Productive cough Diseases 0.000 description 1
• RBQOQRRFDPXAGN-UHFFFAOYSA-N Propentofylline Chemical compound CN1C(=O)N(CCCCC(C)=O)C(=O)C2=C1N=CN2CCC RBQOQRRFDPXAGN-UHFFFAOYSA-N 0.000 description 1
• 208000001431 Psychomotor Agitation Diseases 0.000 description 1
• 208000028017 Psychotic disease Diseases 0.000 description 1
• 206010038743 Restlessness Diseases 0.000 description 1
• 208000034189 Sclerosis Diseases 0.000 description 1
• 238000012300 Sequence Analysis Methods 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
• 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
• 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 206010043114 Tangentiality Diseases 0.000 description 1
• 102000009843 Thyroglobulin Human genes 0.000 description 1
• 108010034949 Thyroglobulin Proteins 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
• 102000007238 Transferrin Receptors Human genes 0.000 description 1
• 108010033576 Transferrin Receptors Proteins 0.000 description 1
• RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
• 206010046865 Vaccinia virus infection Diseases 0.000 description 1
• 206010047513 Vision blurred Diseases 0.000 description 1
• 206010047571 Visual impairment Diseases 0.000 description 1
• 229930003779 Vitamin B12 Natural products 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• FHICGHSMIPIAPL-HDYAAECPSA-N [2-[3-[6-[3-[(5R,6aS,6bR,12aR)-10-[6-[2-[2-[4,5-dihydroxy-3-(3,4,5-trihydroxyoxan-2-yl)oxyoxan-2-yl]ethoxy]ethyl]-3,4,5-trihydroxyoxan-2-yl]oxy-5-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carbonyl]peroxypropyl]-5-[[5-[8-[3,5-dihydroxy-4-(3,4,5-trihydroxyoxan-2-yl)oxyoxan-2-yl]octoxy]-3,4-dihydroxy-6-methyloxan-2-yl]methoxy]-3,4-dihydroxyoxan-2-yl]propoxymethyl]-5-hydroxy-3-[(6S)-6-hydroxy-2,6-dimethylocta-2,7-dienoyl]oxy-6-methyloxan-4-yl] (2E,6S)-6-hydroxy-2-(hydroxymethyl)-6-methylocta-2,7-dienoate Chemical compound C=C[C@@](C)(O)CCC=C(C)C(=O)OC1C(OC(=O)C(\CO)=C\CC[C@](C)(O)C=C)C(O)C(C)OC1COCCCC1C(O)C(O)C(OCC2C(C(O)C(OCCCCCCCCC3C(C(OC4C(C(O)C(O)CO4)O)C(O)CO3)O)C(C)O2)O)C(CCCOOC(=O)C23C(CC(C)(C)CC2)C=2[C@@]([C@]4(C)CCC5C(C)(C)C(OC6C(C(O)C(O)C(CCOCCC7C(C(O)C(O)CO7)OC7C(C(O)C(O)CO7)O)O6)O)CC[C@]5(C)C4CC=2)(C)C[C@H]3O)O1 FHICGHSMIPIAPL-HDYAAECPSA-N 0.000 description 1
• PCBOWMZAEDDKNH-HOTGVXAUSA-N [4-(trifluoromethoxy)phenyl]methyl (3as,6as)-2-(3-fluoro-4-sulfamoylbenzoyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound C1=C(F)C(S(=O)(=O)N)=CC=C1C(=O)N1C[C@H]2CN(C(=O)OCC=3C=CC(OC(F)(F)F)=CC=3)C[C@@H]2C1 PCBOWMZAEDDKNH-HOTGVXAUSA-N 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 229960005327 acemannan Drugs 0.000 description 1
• 238000006640 acetylation reaction Methods 0.000 description 1
• OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
• 229960004373 acetylcholine Drugs 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 230000000240 adjuvant effect Effects 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 230000009824 affinity maturation Effects 0.000 description 1
• 238000005054 agglomeration Methods 0.000 description 1
• 230000004520 agglutination Effects 0.000 description 1
• 230000032683 aging Effects 0.000 description 1
• 238000013019 agitation Methods 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 108090000185 alpha-Synuclein Proteins 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
• ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 210000003484 anatomy Anatomy 0.000 description 1
• 150000001450 anions Chemical class 0.000 description 1
• 239000003529 anticholesteremic agent Substances 0.000 description 1
• 229940127226 anticholesterol agent Drugs 0.000 description 1
• 239000000935 antidepressant agent Substances 0.000 description 1
• 229940005513 antidepressants Drugs 0.000 description 1
• 230000003078 antioxidant effect Effects 0.000 description 1
• 239000000164 antipsychotic agent Substances 0.000 description 1
• 229940005529 antipsychotics Drugs 0.000 description 1
• 230000036506 anxiety Effects 0.000 description 1
• 201000007201 aphasia Diseases 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000012062 aqueous buffer Substances 0.000 description 1
• 229940039856 aricept Drugs 0.000 description 1
• 238000003149 assay kit Methods 0.000 description 1
• 239000003693 atypical antipsychotic agent Substances 0.000 description 1
• 230000002567 autonomic effect Effects 0.000 description 1
• 150000001540 azides Chemical class 0.000 description 1
• 208000022362 bacterial infectious disease Diseases 0.000 description 1
• 230000006399 behavior Effects 0.000 description 1
• 208000013404 behavioral symptom Diseases 0.000 description 1
• 238000009227 behaviour therapy Methods 0.000 description 1
• 108010005774 beta-Galactosidase Proteins 0.000 description 1
• 230000001588 bifunctional effect Effects 0.000 description 1
• 239000012867 bioactive agent Substances 0.000 description 1
• 230000003115 biocidal effect Effects 0.000 description 1
• 239000000560 biocompatible material Substances 0.000 description 1
• 229920002988 biodegradable polymer Polymers 0.000 description 1
• 239000004621 biodegradable polymer Substances 0.000 description 1
• 239000013060 biological fluid Substances 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 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 1
• 210000005013 brain tissue Anatomy 0.000 description 1
• 239000012267 brine Substances 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 1
• 201000011510 cancer Diseases 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
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 230000033077 cellular process Effects 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• 229940048961 cholinesterase Drugs 0.000 description 1
• 229940059329 chondroitin sulfate Drugs 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
• 238000003501 co-culture Methods 0.000 description 1
• FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 description 1
• 231100000876 cognitive deterioration Toxicity 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 229960005188 collagen Drugs 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 238000004590 computer program Methods 0.000 description 1
• IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 1
• 210000002808 connective tissue Anatomy 0.000 description 1
• 108091036078 conserved sequence Proteins 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 230000001934 delay Effects 0.000 description 1
• 238000012217 deletion Methods 0.000 description 1
• 230000037430 deletion Effects 0.000 description 1
• 238000002716 delivery method Methods 0.000 description 1
• 231100000868 delusion Toxicity 0.000 description 1
• 210000001947 dentate gyrus Anatomy 0.000 description 1
• 229960000633 dextran sulfate Drugs 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000000378 dietary effect Effects 0.000 description 1
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
• PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 239000003792 electrolyte Substances 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 210000003989 endothelium vascular Anatomy 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 230000007613 environmental effect Effects 0.000 description 1
• 230000007515 enzymatic degradation Effects 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 229940011871 estrogen Drugs 0.000 description 1
• 239000000262 estrogen Substances 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 229940108366 exelon Drugs 0.000 description 1
• 230000020764 fibrinolysis Effects 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 210000001652 frontal lobe Anatomy 0.000 description 1
• 108010074605 gamma-Globulins Proteins 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 230000007160 gastrointestinal dysfunction Effects 0.000 description 1
• 238000002523 gelfiltration Methods 0.000 description 1
• 238000010353 genetic engineering Methods 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 239000003365 glass fiber Substances 0.000 description 1
• 229940084910 gliadel Drugs 0.000 description 1
• 239000003862 glucocorticoid Substances 0.000 description 1
• AWUCVROLDVIAJX-UHFFFAOYSA-N glycerol 1-phosphate Chemical compound OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
• 125000003827 glycol group Chemical group 0.000 description 1
• 230000003862 health status Effects 0.000 description 1
• 210000002216 heart Anatomy 0.000 description 1
• 230000007686 hepatotoxicity Effects 0.000 description 1
• 231100000304 hepatotoxicity Toxicity 0.000 description 1
• 208000017105 hereditary amyloidosis Diseases 0.000 description 1
• 229920002674 hyaluronan Polymers 0.000 description 1
• 229960003160 hyaluronic acid Drugs 0.000 description 1
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 125000001165 hydrophobic group Chemical group 0.000 description 1
• JGPMMRGNQUBGND-UHFFFAOYSA-N idebenone Chemical compound COC1=C(OC)C(=O)C(CCCCCCCCCCO)=C(C)C1=O JGPMMRGNQUBGND-UHFFFAOYSA-N 0.000 description 1
• 229960004135 idebenone Drugs 0.000 description 1
• 208000009326 ileitis Diseases 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 230000036039 immunity Effects 0.000 description 1
• 230000000984 immunochemical effect Effects 0.000 description 1
• 229940072221 immunoglobulins Drugs 0.000 description 1
• 230000002584 immunomodulator Effects 0.000 description 1
• 238000001114 immunoprecipitation Methods 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 210000003000 inclusion body Anatomy 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 239000011261 inert gas Substances 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 238000011081 inoculation Methods 0.000 description 1
• 206010022437 insomnia Diseases 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 229960000310 isoleucine Drugs 0.000 description 1
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 239000004816 latex Substances 0.000 description 1
• 229920000126 latex Polymers 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 210000004558 lewy body Anatomy 0.000 description 1
• 230000004576 lipid-binding Effects 0.000 description 1
• 230000004303 low vision Effects 0.000 description 1
• 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 210000004880 lymph fluid Anatomy 0.000 description 1
• 235000018977 lysine Nutrition 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 229940092110 macugen Drugs 0.000 description 1
• 238000007726 management method Methods 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 230000013011 mating Effects 0.000 description 1
• 238000010339 medical test Methods 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 238000005374 membrane filtration Methods 0.000 description 1
• 230000007087 memory ability Effects 0.000 description 1
• 206010027175 memory impairment Diseases 0.000 description 1
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
• 239000003094 microcapsule Substances 0.000 description 1
• 230000002025 microglial effect Effects 0.000 description 1
• 238000000386 microscopy Methods 0.000 description 1
• 210000001589 microsome Anatomy 0.000 description 1
• 230000003278 mimic effect Effects 0.000 description 1
• 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
• 210000003097 mucus Anatomy 0.000 description 1
• 230000020763 muscle atrophy Effects 0.000 description 1
• 210000000663 muscle cell Anatomy 0.000 description 1
• 201000000585 muscular atrophy Diseases 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• 210000001087 myotubule Anatomy 0.000 description 1
• OKPYIWASQZGASP-UHFFFAOYSA-N n-(2-hydroxypropyl)-2-methylprop-2-enamide Chemical compound CC(O)CNC(=O)C(C)=C OKPYIWASQZGASP-UHFFFAOYSA-N 0.000 description 1
• 229940033872 namenda Drugs 0.000 description 1
• 239000013642 negative control Substances 0.000 description 1
• 210000005036 nerve Anatomy 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 210000002241 neurite Anatomy 0.000 description 1
• 230000004770 neurodegeneration Effects 0.000 description 1
• 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
• 230000016273 neuron death Effects 0.000 description 1
• 239000002547 new drug Substances 0.000 description 1
• 229960003512 nicotinic acid Drugs 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 229910052757 nitrogen Inorganic materials 0.000 description 1
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 239000000346 nonvolatile oil Substances 0.000 description 1
• 102000039446 nucleic acids Human genes 0.000 description 1
• 108020004707 nucleic acids Proteins 0.000 description 1
• 150000007523 nucleic acids Chemical class 0.000 description 1
• 235000015097 nutrients Nutrition 0.000 description 1
• 229920001778 nylon Polymers 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 238000002577 ophthalmoscopy Methods 0.000 description 1
• 208000020911 optic nerve disease Diseases 0.000 description 1
• 229940126701 oral medication Drugs 0.000 description 1
• 150000002895 organic esters Chemical class 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 229940092253 ovalbumin Drugs 0.000 description 1
• 238000007500 overflow downdraw method Methods 0.000 description 1
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
• 230000026792 palmitoylation Effects 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 229940005014 pegaptanib sodium Drugs 0.000 description 1
• 229940111202 pepsin Drugs 0.000 description 1
• 108010091748 peptide A Proteins 0.000 description 1
• LQRJAEQXMSMEDP-XCHBZYMASA-N peptide a Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)NCCCC[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)C(\NC(=O)[C@@H](CCCCN)NC(=O)CNC(C)=O)=C/C=1C=CC=CC=1)C(N)=O)C(=O)C(\NC(=O)[C@@H](CCCCN)NC(=O)CNC(C)=O)=C\C1=CC=CC=C1 LQRJAEQXMSMEDP-XCHBZYMASA-N 0.000 description 1
• KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 230000008823 permeabilization Effects 0.000 description 1
• 238000002823 phage display Methods 0.000 description 1
• 239000008024 pharmaceutical diluent Substances 0.000 description 1
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
• XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
• 230000000649 photocoagulation Effects 0.000 description 1
• 238000002428 photodynamic therapy Methods 0.000 description 1
• 108091008695 photoreceptors Proteins 0.000 description 1
• 239000000902 placebo Substances 0.000 description 1
• 229940068196 placebo Drugs 0.000 description 1
• 230000007406 plaque accumulation Effects 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
• 229920000768 polyamine Polymers 0.000 description 1
• 229920000728 polyester Polymers 0.000 description 1
• 229920002098 polyfluorene Polymers 0.000 description 1
• 239000010318 polygalacturonic acid Substances 0.000 description 1
• 239000004633 polyglycolic acid Substances 0.000 description 1
• 229920002704 polyhistidine Polymers 0.000 description 1
• 230000000379 polymerizing effect Effects 0.000 description 1
• 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
• 229920002635 polyurethane Polymers 0.000 description 1
• 239000004814 polyurethane Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000011148 porous material Substances 0.000 description 1
• 108020001213 potassium channel Proteins 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 238000004094 preconcentration Methods 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 230000002028 premature Effects 0.000 description 1
• 230000037452 priming Effects 0.000 description 1
• 230000004647 pro-inflammatory pathway Effects 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• 208000037821 progressive disease Diseases 0.000 description 1
• 229960002934 propentofylline Drugs 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
• 108020001775 protein parts Proteins 0.000 description 1
• 230000006337 proteolytic cleavage Effects 0.000 description 1
• 238000005086 pumping Methods 0.000 description 1
• 238000003127 radioimmunoassay Methods 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 230000006798 recombination Effects 0.000 description 1
• 238000005215 recombination Methods 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 230000002207 retinal effect Effects 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 210000003296 saliva Anatomy 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 238000011896 sensitive detection Methods 0.000 description 1
• 239000012679 serum free medium Substances 0.000 description 1
• 230000001568 sexual effect Effects 0.000 description 1
• 238000004904 shortening Methods 0.000 description 1
• 208000019116 sleep disease Diseases 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 1
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 238000010532 solid phase synthesis reaction Methods 0.000 description 1
• 210000003802 sputum Anatomy 0.000 description 1
• 208000024794 sputum Diseases 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 230000035882 stress Effects 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 239000002344 surface layer Substances 0.000 description 1
• 230000000946 synaptic effect Effects 0.000 description 1
• 230000005062 synaptic transmission Effects 0.000 description 1
• 229920001059 synthetic polymer Polymers 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 210000003478 temporal lobe Anatomy 0.000 description 1
• 239000012085 test solution Substances 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 229940126585 therapeutic drug Drugs 0.000 description 1
• 229960002175 thyroglobulin Drugs 0.000 description 1
• 239000012581 transferrin Substances 0.000 description 1
• 230000014616 translation Effects 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
• 201000008827 tuberculosis Diseases 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• 208000007089 vaccinia Diseases 0.000 description 1
• 229940102566 valproate Drugs 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 238000012795 verification Methods 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 208000029257 vision disease Diseases 0.000 description 1
• 230000004304 visual acuity Effects 0.000 description 1
• 230000000007 visual effect Effects 0.000 description 1
• 235000019163 vitamin B12 Nutrition 0.000 description 1
• 239000011715 vitamin B12 Substances 0.000 description 1
• 230000004580 weight loss Effects 0.000 description 1
• 238000001238 wet grinding Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 210000004885 white matter Anatomy 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1