CA2408925A1 - Synthetic immunogenic but non-amyloidogenic peptides homologous to amyloid beta for induction of an immune response to amyloid beta and amyloid deposits - Google Patents
Synthetic immunogenic but non-amyloidogenic peptides homologous to amyloid beta for induction of an immune response to amyloid beta and amyloid deposits Download PDFInfo
- Publication number
- CA2408925A1 CA2408925A1 CA002408925A CA2408925A CA2408925A1 CA 2408925 A1 CA2408925 A1 CA 2408925A1 CA 002408925 A CA002408925 A CA 002408925A CA 2408925 A CA2408925 A CA 2408925A CA 2408925 A1 CA2408925 A1 CA 2408925A1
- Authority
- CA
- Canada
- Prior art keywords
- peptide
- seq
- xaa
- amyloid
- residues
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 218
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 99
- 208000037259 Amyloid Plaque Diseases 0.000 title claims abstract description 28
- 230000028993 immune response Effects 0.000 title claims abstract description 23
- 230000002163 immunogen Effects 0.000 title abstract description 30
- 108010048112 Amyloidogenic Proteins Proteins 0.000 title abstract description 21
- 102000009091 Amyloidogenic Proteins Human genes 0.000 title abstract description 21
- 230000003942 amyloidogenic effect Effects 0.000 title abstract description 18
- 102000013455 Amyloid beta-Peptides Human genes 0.000 title description 8
- 108010090849 Amyloid beta-Peptides Proteins 0.000 title description 8
- 230000006698 induction Effects 0.000 title description 5
- 230000003053 immunization Effects 0.000 claims abstract description 36
- 239000000203 mixture Substances 0.000 claims abstract description 28
- 230000001939 inductive effect Effects 0.000 claims abstract description 4
- 239000002671 adjuvant Substances 0.000 claims description 37
- 238000000034 method Methods 0.000 claims description 37
- 239000000427 antigen Substances 0.000 claims description 28
- 108091007433 antigens Proteins 0.000 claims description 28
- 102000036639 antigens Human genes 0.000 claims description 28
- 230000003941 amyloidogenesis Effects 0.000 claims description 20
- 210000002443 helper t lymphocyte Anatomy 0.000 claims description 14
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 13
- 229920000642 polymer Polymers 0.000 claims description 10
- 229940037003 alum Drugs 0.000 claims description 8
- 239000012752 auxiliary agent Substances 0.000 claims description 6
- 125000001433 C-terminal amino-acid group Chemical group 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 241000024188 Andala Species 0.000 claims description 4
- 241000712079 Measles morbillivirus Species 0.000 claims description 4
- 235000018417 cysteine Nutrition 0.000 claims description 4
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 241000700721 Hepatitis B virus Species 0.000 claims description 3
- 108010081690 Pertussis Toxin Proteins 0.000 claims description 3
- 108010055044 Tetanus Toxin Proteins 0.000 claims description 3
- 229940118376 tetanus toxin Drugs 0.000 claims description 3
- 241000606161 Chlamydia Species 0.000 claims description 2
- 108010053187 Diphtheria Toxin Proteins 0.000 claims description 2
- 102000016607 Diphtheria Toxin Human genes 0.000 claims description 2
- 229920001503 Glucan Polymers 0.000 claims description 2
- 101710164702 Major outer membrane protein Proteins 0.000 claims description 2
- 229920000057 Mannan Polymers 0.000 claims description 2
- 241000223960 Plasmodium falciparum Species 0.000 claims description 2
- 101000801721 Schistosoma mansoni Triosephosphate isomerase Proteins 0.000 claims description 2
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 claims description 2
- 230000003308 immunostimulating effect Effects 0.000 abstract description 7
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 41
- 208000024827 Alzheimer disease Diseases 0.000 description 34
- 241000699670 Mus sp. Species 0.000 description 34
- 210000004027 cell Anatomy 0.000 description 28
- 125000000539 amino acid group Chemical group 0.000 description 23
- 210000004556 brain Anatomy 0.000 description 22
- 238000010186 staining Methods 0.000 description 22
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 21
- 230000002829 reductive effect Effects 0.000 description 21
- 108090000623 proteins and genes Proteins 0.000 description 20
- 230000015572 biosynthetic process Effects 0.000 description 19
- 238000002649 immunization Methods 0.000 description 19
- 235000018102 proteins Nutrition 0.000 description 19
- 102000004169 proteins and genes Human genes 0.000 description 19
- 241001465754 Metazoa Species 0.000 description 18
- 108010039918 Polylysine Proteins 0.000 description 18
- 229920000656 polylysine Polymers 0.000 description 18
- 229960005486 vaccine Drugs 0.000 description 17
- 102000000589 Interleukin-1 Human genes 0.000 description 16
- 108010002352 Interleukin-1 Proteins 0.000 description 16
- 108010064470 polyaspartate Proteins 0.000 description 16
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 15
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 15
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 15
- 210000004899 c-terminal region Anatomy 0.000 description 15
- 238000000338 in vitro Methods 0.000 description 15
- 241000699666 Mus <mouse, genus> Species 0.000 description 14
- 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 14
- 231100000331 toxic Toxicity 0.000 description 14
- 230000002588 toxic effect Effects 0.000 description 14
- MQWISMJKHOUEMW-ULQDDVLXSA-N Phe-Arg-His Chemical compound C([C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CC=CC=C1 MQWISMJKHOUEMW-ULQDDVLXSA-N 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 230000009467 reduction Effects 0.000 description 13
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 12
- IDQNVIWPPWAFSY-AVGNSLFASA-N His-His-Gln Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(N)=O)C(O)=O IDQNVIWPPWAFSY-AVGNSLFASA-N 0.000 description 12
- XMBSYZWANAQXEV-UHFFFAOYSA-N N-alpha-L-glutamyl-L-phenylalanine Natural products OC(=O)CCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XMBSYZWANAQXEV-UHFFFAOYSA-N 0.000 description 12
- XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 description 12
- 108010087823 glycyltyrosine Proteins 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- 238000002255 vaccination Methods 0.000 description 12
- XEDQMTWEYFBOIK-ACZMJKKPSA-N Asp-Ala-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O XEDQMTWEYFBOIK-ACZMJKKPSA-N 0.000 description 11
- KGHLGJAXYSVNJP-WHFBIAKZSA-N Asp-Ser-Gly Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O KGHLGJAXYSVNJP-WHFBIAKZSA-N 0.000 description 11
- WATXSTJXNBOHKD-LAEOZQHASA-N Glu-Asp-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O WATXSTJXNBOHKD-LAEOZQHASA-N 0.000 description 11
- IALQAMYQJBZNSK-WHFBIAKZSA-N Gly-Ser-Asn Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O IALQAMYQJBZNSK-WHFBIAKZSA-N 0.000 description 11
- UNUZEBFXGWVAOP-DZKIICNBSA-N Tyr-Glu-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O UNUZEBFXGWVAOP-DZKIICNBSA-N 0.000 description 11
- 206010002022 amyloidosis Diseases 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 238000002983 circular dichroism Methods 0.000 description 11
- 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 11
- 230000003993 interaction Effects 0.000 description 11
- 210000000274 microglia Anatomy 0.000 description 11
- 241000282412 Homo Species 0.000 description 10
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 10
- 235000001014 amino acid Nutrition 0.000 description 10
- 230000035557 fibrillogenesis Effects 0.000 description 10
- 230000002209 hydrophobic effect Effects 0.000 description 10
- 230000005847 immunogenicity Effects 0.000 description 10
- 238000011534 incubation Methods 0.000 description 10
- 239000011859 microparticle Substances 0.000 description 10
- 238000011830 transgenic mouse model Methods 0.000 description 10
- ITWQLSZTLBKWJM-YUMQZZPRSA-N Lys-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CCCCN ITWQLSZTLBKWJM-YUMQZZPRSA-N 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 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 9
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 8
- 150000001413 amino acids Chemical class 0.000 description 8
- 230000000890 antigenic effect Effects 0.000 description 8
- 238000013459 approach Methods 0.000 description 8
- 230000002490 cerebral effect Effects 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 210000001744 T-lymphocyte Anatomy 0.000 description 7
- 230000002776 aggregation Effects 0.000 description 7
- 238000004220 aggregation Methods 0.000 description 7
- 108010008685 alanyl-glutamyl-aspartic acid Proteins 0.000 description 7
- 230000008499 blood brain barrier function Effects 0.000 description 7
- 210000001218 blood-brain barrier Anatomy 0.000 description 7
- -1 cationic amino acid Chemical group 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 231100000252 nontoxic Toxicity 0.000 description 7
- 230000003000 nontoxic effect Effects 0.000 description 7
- 239000002243 precursor Substances 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 108010014765 tomato lectin Proteins 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- 102000001049 Amyloid Human genes 0.000 description 6
- 108010094108 Amyloid Proteins 0.000 description 6
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 6
- 241000699660 Mus musculus Species 0.000 description 6
- 206010029350 Neurotoxicity Diseases 0.000 description 6
- 206010044221 Toxic encephalopathy Diseases 0.000 description 6
- 230000001054 cortical effect Effects 0.000 description 6
- 230000008021 deposition Effects 0.000 description 6
- 230000002600 fibrillogenic effect Effects 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 230000002025 microglial effect Effects 0.000 description 6
- 230000001537 neural effect Effects 0.000 description 6
- 230000007135 neurotoxicity Effects 0.000 description 6
- 231100000228 neurotoxicity Toxicity 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 230000003389 potentiating effect Effects 0.000 description 6
- 102100039289 Glial fibrillary acidic protein Human genes 0.000 description 5
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 5
- 229920002971 Heparan sulfate Polymers 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 206010029260 Neuroblastoma Diseases 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- ZHAFUINZIZIXFC-UHFFFAOYSA-N [9-(dimethylamino)-10-methylbenzo[a]phenoxazin-5-ylidene]azanium;chloride Chemical compound [Cl-].O1C2=CC(=[NH2+])C3=CC=CC=C3C2=NC2=C1C=C(N(C)C)C(C)=C2 ZHAFUINZIZIXFC-UHFFFAOYSA-N 0.000 description 5
- 210000003719 b-lymphocyte Anatomy 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 5
- 230000000971 hippocampal effect Effects 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 230000003902 lesion Effects 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 5
- 230000007171 neuropathology Effects 0.000 description 5
- 230000000242 pagocytic effect Effects 0.000 description 5
- 229930182490 saponin Natural products 0.000 description 5
- 150000007949 saponins Chemical class 0.000 description 5
- 235000017709 saponins Nutrition 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- SICITCLFXRGKJW-IIZANFQQSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2,6-diaminohexanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoic acid Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)[C@@H](N)CCCCN)CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 SICITCLFXRGKJW-IIZANFQQSA-N 0.000 description 4
- KXEVYGKATAMXJJ-ACZMJKKPSA-N Ala-Glu-Asp Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O KXEVYGKATAMXJJ-ACZMJKKPSA-N 0.000 description 4
- 102100029470 Apolipoprotein E Human genes 0.000 description 4
- 101710095339 Apolipoprotein E Proteins 0.000 description 4
- NYGILGUOUOXGMJ-YUMQZZPRSA-N Asn-Lys-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O NYGILGUOUOXGMJ-YUMQZZPRSA-N 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- 101710198693 Invasin Proteins 0.000 description 4
- 238000000134 MTT assay Methods 0.000 description 4
- 231100000002 MTT assay Toxicity 0.000 description 4
- 241001529936 Murinae Species 0.000 description 4
- 206010029240 Neuritis Diseases 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- LAYSXAOGWHKNED-XPUUQOCRSA-N Val-Gly-Ser Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O LAYSXAOGWHKNED-XPUUQOCRSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 210000001130 astrocyte Anatomy 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 239000002158 endotoxin Substances 0.000 description 4
- 238000007421 fluorometric assay Methods 0.000 description 4
- 102000006495 integrins Human genes 0.000 description 4
- 108010044426 integrins Proteins 0.000 description 4
- 229920006008 lipopolysaccharide Polymers 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 238000001543 one-way ANOVA Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 230000032258 transport Effects 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 108010042708 Acetylmuramyl-Alanyl-Isoglutamine Proteins 0.000 description 3
- 206010002023 Amyloidoses Diseases 0.000 description 3
- 108010071619 Apolipoproteins Proteins 0.000 description 3
- 102000007592 Apolipoproteins Human genes 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 101100440173 Mus musculus Clu gene Proteins 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000005875 antibody response Effects 0.000 description 3
- 210000000612 antigen-presenting cell Anatomy 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 238000007405 data analysis Methods 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 230000012202 endocytosis Effects 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 3
- 210000001320 hippocampus Anatomy 0.000 description 3
- 230000005745 host immune response Effects 0.000 description 3
- 210000004408 hybridoma Anatomy 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- BSOQXXWZTUDTEL-ZUYCGGNHSA-N muramyl dipeptide Chemical compound OC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)O[C@@H](O)[C@@H]1NC(C)=O BSOQXXWZTUDTEL-ZUYCGGNHSA-N 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 102000013415 peroxidase activity proteins Human genes 0.000 description 3
- 108040007629 peroxidase activity proteins Proteins 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 235000013930 proline Nutrition 0.000 description 3
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001228 trophic effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 229910001868 water Inorganic materials 0.000 description 3
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 2
- KJDSORYAHBAGPP-UHFFFAOYSA-N 4-(3,4-diaminophenyl)benzene-1,2-diamine;hydron;tetrachloride Chemical compound Cl.Cl.Cl.Cl.C1=C(N)C(N)=CC=C1C1=CC=C(N)C(N)=C1 KJDSORYAHBAGPP-UHFFFAOYSA-N 0.000 description 2
- 235000005749 Anthriscus sylvestris Nutrition 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- 201000010374 Down Syndrome Diseases 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 description 2
- ZZLWLWSUIBSMNP-CIUDSAMLSA-N His-Asp-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O ZZLWLWSUIBSMNP-CIUDSAMLSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 108090001090 Lectins Proteins 0.000 description 2
- 102000004856 Lectins Human genes 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 208000026139 Memory disease Diseases 0.000 description 2
- KFEUJDWYNGMDBV-LODBTCKLSA-N N-acetyllactosamine Chemical group O[C@@H]1[C@@H](NC(=O)C)[C@H](O)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KFEUJDWYNGMDBV-LODBTCKLSA-N 0.000 description 2
- 108010084333 N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 101710116435 Outer membrane protein Proteins 0.000 description 2
- 201000005702 Pertussis Diseases 0.000 description 2
- 206010057249 Phagocytosis Diseases 0.000 description 2
- 102100022033 Presenilin-1 Human genes 0.000 description 2
- 108010036933 Presenilin-1 Proteins 0.000 description 2
- 102000029797 Prion Human genes 0.000 description 2
- 108091000054 Prion Proteins 0.000 description 2
- 108010067787 Proteoglycans Proteins 0.000 description 2
- 102000016611 Proteoglycans Human genes 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 108700005078 Synthetic Genes Proteins 0.000 description 2
- 230000024932 T cell mediated immunity Effects 0.000 description 2
- 206010043376 Tetanus Diseases 0.000 description 2
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 2
- 206010044688 Trisomy 21 Diseases 0.000 description 2
- DHINLYMWMXQGMQ-IHRRRGAJSA-N Val-His-His Chemical compound C([C@H](NC(=O)[C@@H](N)C(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CN=CN1 DHINLYMWMXQGMQ-IHRRRGAJSA-N 0.000 description 2
- 241000607734 Yersinia <bacteria> Species 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 108010005233 alanylglutamic acid Proteins 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 101150031224 app gene Proteins 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 238000001142 circular dichroism spectrum Methods 0.000 description 2
- 230000007370 cognitive improvement Effects 0.000 description 2
- 239000002577 cryoprotective agent Substances 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 206010013023 diphtheria Diseases 0.000 description 2
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
- 230000002900 effect on cell Effects 0.000 description 2
- 238000001493 electron microscopy Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 210000000224 granular leucocyte Anatomy 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 239000011539 homogenization buffer Substances 0.000 description 2
- 230000028996 humoral immune response Effects 0.000 description 2
- 238000010191 image analysis Methods 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000002523 lectin Substances 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 108010091617 pentalysine Proteins 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 210000001539 phagocyte Anatomy 0.000 description 2
- 230000008782 phagocytosis Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 230000007505 plaque formation Effects 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 238000013105 post hoc analysis Methods 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 150000003148 prolines Chemical class 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000003118 sandwich ELISA Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 229940031439 squalene Drugs 0.000 description 2
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 230000007470 synaptic degeneration Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- RALAXQOLLAQGTI-IRGGMKSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-1-[(2s)-2-amino-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]butanedioic acid Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(O)=O)C(O)=O)CC1=CC=CC=C1 RALAXQOLLAQGTI-IRGGMKSGSA-N 0.000 description 1
- JJWFIVDAMOFNPS-QRPNPIFTSA-N (2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;hydrochloride Chemical group Cl.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 JJWFIVDAMOFNPS-QRPNPIFTSA-N 0.000 description 1
- VHUVBWVDIFVVBI-SNYZSRNZSA-N (2s)-3-(4-hydroxyphenyl)-2-(octadecylamino)propanoic acid;hydrochloride Chemical compound Cl.CCCCCCCCCCCCCCCCCCN[C@H](C(O)=O)CC1=CC=C(O)C=C1 VHUVBWVDIFVVBI-SNYZSRNZSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- CXENHBSYCFFKJS-OXYODPPFSA-N (Z,E)-alpha-farnesene Chemical compound CC(C)=CCC\C(C)=C\C\C=C(\C)C=C CXENHBSYCFFKJS-OXYODPPFSA-N 0.000 description 1
- 230000006269 (delayed) early viral mRNA transcription Effects 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical class O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- PDQGEKGUTOTUNV-TZSSRYMLSA-N 4'-deoxy-4'-iododoxorubicin 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(=O)CO)[C@H]1C[C@H](N)[C@H](I)[C@H](C)O1 PDQGEKGUTOTUNV-TZSSRYMLSA-N 0.000 description 1
- YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
- 208000023761 AL amyloidosis Diseases 0.000 description 1
- 238000010175 APPswe/PSEN1dE9 Methods 0.000 description 1
- NHCPCLJZRSIDHS-ZLUOBGJFSA-N Ala-Asp-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O NHCPCLJZRSIDHS-ZLUOBGJFSA-N 0.000 description 1
- FBHOPGDGELNWRH-DRZSPHRISA-N Ala-Glu-Phe Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O FBHOPGDGELNWRH-DRZSPHRISA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 241000252073 Anguilliformes Species 0.000 description 1
- 108010087765 Antipain Proteins 0.000 description 1
- OGUPCHKBOKJFMA-SRVKXCTJSA-N Arg-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N OGUPCHKBOKJFMA-SRVKXCTJSA-N 0.000 description 1
- BMNVSPMWMICFRV-DCAQKATOSA-N Arg-His-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(O)=O)C(O)=O)CC1=CN=CN1 BMNVSPMWMICFRV-DCAQKATOSA-N 0.000 description 1
- GYWQGGUCMDCUJE-DLOVCJGASA-N Asp-Phe-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(O)=O GYWQGGUCMDCUJE-DLOVCJGASA-N 0.000 description 1
- DWBZEJHQQIURML-IMJSIDKUSA-N Asp-Ser Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(O)=O DWBZEJHQQIURML-IMJSIDKUSA-N 0.000 description 1
- 102100036597 Basement membrane-specific heparan sulfate proteoglycan core protein Human genes 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 1
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 description 1
- 108090000197 Clusterin Proteins 0.000 description 1
- 102000003780 Clusterin Human genes 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 108010078015 Complement C3b Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 208000031124 Dementia Alzheimer type Diseases 0.000 description 1
- 238000001061 Dunnett's test Methods 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 101100425960 Escherichia coli traT gene Proteins 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 238000000305 Fourier transform infrared microscopy Methods 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000004878 Gelsolin Human genes 0.000 description 1
- 108090001064 Gelsolin Proteins 0.000 description 1
- 206010018341 Gliosis Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- PMSMKNYRZCKVMC-DRZSPHRISA-N Glu-Phe-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)N PMSMKNYRZCKVMC-DRZSPHRISA-N 0.000 description 1
- KJBGAZSLZAQDPV-KKUMJFAQSA-N Glu-Phe-Arg Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CCC(=O)O)N KJBGAZSLZAQDPV-KKUMJFAQSA-N 0.000 description 1
- ZALGPUWUVHOGAE-GVXVVHGQSA-N Glu-Val-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZALGPUWUVHOGAE-GVXVVHGQSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- PYTZFYUXZZHOAD-WHFBIAKZSA-N Gly-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)CN PYTZFYUXZZHOAD-WHFBIAKZSA-N 0.000 description 1
- MVORZMQFXBLMHM-QWRGUYRKSA-N Gly-His-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CN=CN1 MVORZMQFXBLMHM-QWRGUYRKSA-N 0.000 description 1
- XBGGUPMXALFZOT-VIFPVBQESA-N Gly-Tyr Chemical compound NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-VIFPVBQESA-N 0.000 description 1
- UVTSZKIATYSKIR-RYUDHWBXSA-N Gly-Tyr-Glu Chemical compound [H]NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O UVTSZKIATYSKIR-RYUDHWBXSA-N 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical class OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 108010010234 HDL Lipoproteins Proteins 0.000 description 1
- 102000015779 HDL Lipoproteins Human genes 0.000 description 1
- 108010022901 Heparin Lyase Proteins 0.000 description 1
- 229940124872 Hepatitis B virus vaccine Drugs 0.000 description 1
- SWSVTNGMKBDTBM-DCAQKATOSA-N His-Gln-Glu Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N SWSVTNGMKBDTBM-DCAQKATOSA-N 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 1
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 1
- 101000909811 Homo sapiens Protein cornichon homolog 2 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 206010022941 Iridocyclitis Diseases 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 102000007547 Laminin Human genes 0.000 description 1
- 108010085895 Laminin Proteins 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
- 108010028921 Lipopeptides Proteins 0.000 description 1
- GPJGFSFYBJGYRX-YUMQZZPRSA-N Lys-Gly-Asp Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O GPJGFSFYBJGYRX-YUMQZZPRSA-N 0.000 description 1
- MUXNCRWTWBMNHX-SRVKXCTJSA-N Lys-Leu-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O MUXNCRWTWBMNHX-SRVKXCTJSA-N 0.000 description 1
- SKRGVGLIRUGANF-AVGNSLFASA-N Lys-Leu-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O SKRGVGLIRUGANF-AVGNSLFASA-N 0.000 description 1
- ALGGDNMLQNFVIZ-SRVKXCTJSA-N Lys-Lys-Asp Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)O)N ALGGDNMLQNFVIZ-SRVKXCTJSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102000043131 MHC class II family Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 208000005647 Mumps Diseases 0.000 description 1
- 101100293261 Mus musculus Naa15 gene Proteins 0.000 description 1
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 1
- 101150082943 NAT1 gene Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- JKJSIYKSGIDHPM-WBAXXEDZSA-N Phe-Phe-Ala Chemical compound C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](N)Cc1ccccc1)C(O)=O JKJSIYKSGIDHPM-WBAXXEDZSA-N 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
- 108010036908 Presenilin-2 Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 102100024446 Protein cornichon homolog 2 Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- OQPNSDWGAMFJNU-QWRGUYRKSA-N Ser-Gly-Tyr Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 OQPNSDWGAMFJNU-QWRGUYRKSA-N 0.000 description 1
- 108010045517 Serum Amyloid P-Component Proteins 0.000 description 1
- 208000002704 Sporadic Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 238000003639 Student–Newman–Keuls (SNK) method Methods 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 102000004874 Synaptophysin Human genes 0.000 description 1
- 108090001076 Synaptophysin Proteins 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 102100033130 T-box transcription factor T Human genes 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 1
- KSFXWENSJABBFI-ZKWXMUAHSA-N Val-Ser-Asn Chemical compound [H]N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O KSFXWENSJABBFI-ZKWXMUAHSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 108010021836 Yersinia invasin Proteins 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 239000002251 absorbable suture material Substances 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 108010041407 alanylaspartic acid Proteins 0.000 description 1
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 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
- 230000007791 alzheimer disease like pathology Effects 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- DAPUDVOJPZKTSI-UHFFFAOYSA-L ammonium nickel sulfate Chemical compound [NH4+].[NH4+].[Ni+2].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O DAPUDVOJPZKTSI-UHFFFAOYSA-L 0.000 description 1
- 210000004727 amygdala Anatomy 0.000 description 1
- 108010000737 amyloid enhancing factor Proteins 0.000 description 1
- 230000006933 amyloid-beta aggregation Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 201000004612 anterior uveitis Diseases 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- SDNYTAYICBFYFH-TUFLPTIASA-N antipain Chemical compound NC(N)=NCCC[C@@H](C=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SDNYTAYICBFYFH-TUFLPTIASA-N 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 1
- 208000037875 astrocytosis Diseases 0.000 description 1
- 230000007341 astrogliosis Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 239000003541 chymotrypsin inhibitor Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 230000009073 conformational modification Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 210000000877 corpus callosum Anatomy 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 210000001947 dentate gyrus Anatomy 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 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 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000005014 ectopic expression Effects 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 230000002121 endocytic effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 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 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000003619 fibrillary effect Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 238000012252 genetic analysis Methods 0.000 description 1
- 102000054766 genetic haplotypes Human genes 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 230000001434 glomerular Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
- 125000003712 glycosamine group Chemical group 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 108010038983 glycyl-histidyl-lysine Proteins 0.000 description 1
- 238000009499 grossing Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000004326 gyrus cinguli Anatomy 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 108010038082 heparin proteoglycan Proteins 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 231100000171 higher toxicity Toxicity 0.000 description 1
- 108010028295 histidylhistidine Proteins 0.000 description 1
- 108010092508 horseradish peroxidase-polylysine conjugate Proteins 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 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
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000001571 immunoadjuvant effect Effects 0.000 description 1
- 239000000568 immunological adjuvant Substances 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000003960 inflammatory cascade Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000018276 interleukin-1 production Effects 0.000 description 1
- 210000003963 intermediate filament Anatomy 0.000 description 1
- 230000009878 intermolecular interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000004989 laser desorption mass spectroscopy Methods 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 108010052968 leupeptin Proteins 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
- 230000000670 limiting effect Effects 0.000 description 1
- 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 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 210000003071 memory t lymphocyte Anatomy 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000006724 microglial activation Effects 0.000 description 1
- 230000007382 microglial process Effects 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 208000010805 mumps infectious disease Diseases 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 230000006911 nucleation Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 150000007523 nucleic acids Chemical group 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000003024 peritoneal macrophage Anatomy 0.000 description 1
- 108010049224 perlecan Proteins 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 238000001907 polarising light microscopy Methods 0.000 description 1
- 229920000740 poly(D-lysine) polymer Polymers 0.000 description 1
- 229920000724 poly(L-arginine) polymer Polymers 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 108010011110 polyarginine Proteins 0.000 description 1
- 210000004896 polypeptide structure Anatomy 0.000 description 1
- 238000011886 postmortem examination Methods 0.000 description 1
- 231100000316 potential neurotoxicity Toxicity 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000013391 scatchard analysis Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 230000009919 sequestration Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 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
- 230000000638 stimulation Effects 0.000 description 1
- 239000011550 stock 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
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960000814 tetanus toxoid Drugs 0.000 description 1
- 229960002766 tetanus vaccines Drugs 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
- 238000011200 topical administration Methods 0.000 description 1
- 238000002723 toxicity assay Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4711—Alzheimer's disease; Amyloid plaque core protein
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Diabetes (AREA)
- Psychiatry (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US20557800P | 2000-05-22 | 2000-05-22 | |
| US60/205,578 | 2000-05-22 | ||
| PCT/US2001/016322 WO2001090182A2 (en) | 2000-05-22 | 2001-05-22 | Synthetic immunogenic but non-amyloidogenic peptides homologous to amyloid beta for induction of an immune response to amyloid beta and amyloid deposits |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2408925A1 true CA2408925A1 (en) | 2001-11-29 |
Family
ID=22762767
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002408925A Abandoned CA2408925A1 (en) | 2000-05-22 | 2001-05-22 | Synthetic immunogenic but non-amyloidogenic peptides homologous to amyloid beta for induction of an immune response to amyloid beta and amyloid deposits |
Country Status (14)
| Country | Link |
|---|---|
| US (3) | US6713450B2 (enExample) |
| EP (1) | EP1284998B1 (enExample) |
| JP (1) | JP2003534351A (enExample) |
| CN (1) | CN1249085C (enExample) |
| AT (1) | ATE286072T1 (enExample) |
| AU (2) | AU2001274873B2 (enExample) |
| CA (1) | CA2408925A1 (enExample) |
| DE (1) | DE60108111T2 (enExample) |
| ES (1) | ES2238049T3 (enExample) |
| IL (2) | IL152625A0 (enExample) |
| NZ (1) | NZ521939A (enExample) |
| PT (1) | PT1284998E (enExample) |
| WO (1) | WO2001090182A2 (enExample) |
| ZA (1) | ZA200207992B (enExample) |
Families Citing this family (73)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6923964B1 (en) | 1997-12-02 | 2005-08-02 | Neuralab Limited | Active immunization of AScr for prion disorders |
| US7588766B1 (en) | 2000-05-26 | 2009-09-15 | Elan Pharma International Limited | Treatment of amyloidogenic disease |
| US6743427B1 (en) | 1997-12-02 | 2004-06-01 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
| US7790856B2 (en) | 1998-04-07 | 2010-09-07 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize beta amyloid peptide |
| US6913745B1 (en) | 1997-12-02 | 2005-07-05 | Neuralab Limited | Passive immunization of Alzheimer's disease |
| US7179892B2 (en) * | 2000-12-06 | 2007-02-20 | Neuralab Limited | Humanized antibodies that recognize beta amyloid peptide |
| US7964192B1 (en) | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
| US6750324B1 (en) | 1997-12-02 | 2004-06-15 | Neuralab Limited | Humanized and chimeric N-terminal amyloid beta-antibodies |
| US6761888B1 (en) | 2000-05-26 | 2004-07-13 | Neuralab Limited | Passive immunization treatment of Alzheimer's disease |
| TWI239847B (en) * | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
| US20080050367A1 (en) * | 1998-04-07 | 2008-02-28 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
| US6787523B1 (en) * | 1997-12-02 | 2004-09-07 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
| US20030147882A1 (en) * | 1998-05-21 | 2003-08-07 | Alan Solomon | Methods for amyloid removal using anti-amyloid antibodies |
| US7148324B1 (en) * | 1998-12-14 | 2006-12-12 | Dendreon Corporation | Compositions and methods for enhancement of major histocompatibility complex class I restricted antigen presentation |
| US6787637B1 (en) | 1999-05-28 | 2004-09-07 | Neuralab Limited | N-Terminal amyloid-β antibodies |
| UA81216C2 (en) | 1999-06-01 | 2007-12-25 | Prevention and treatment of amyloid disease | |
| ES2248283T3 (es) * | 2000-02-21 | 2006-03-16 | Pharmexa A/S | Nuevo procedimiento para reducir los niveles de amiloide. |
| CZ20022748A3 (cs) * | 2000-02-21 | 2004-03-17 | Pharmexa A/S | Nová metoda regulace obsahu amyloidu |
| WO2002003911A2 (en) | 2000-07-07 | 2002-01-17 | Lars Lannfelt | Prevention and treatment of alzheimer's disease |
| US7700751B2 (en) | 2000-12-06 | 2010-04-20 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize β-amyloid peptide |
| TWI255272B (en) * | 2000-12-06 | 2006-05-21 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
| US7097837B2 (en) * | 2001-02-19 | 2006-08-29 | Pharmexa A/S | Synthetic vaccine agents |
| US20040191264A1 (en) * | 2001-02-19 | 2004-09-30 | Nielsen Klaus Gregorius | Synthetic vaccine agents |
| US6815175B2 (en) | 2001-03-16 | 2004-11-09 | Cornell Research Foundation, Inc. | Anti-amyloid peptide antibody based diagnosis and treatment of a neurological disease or disorder |
| WO2002074931A2 (en) * | 2001-03-20 | 2002-09-26 | University Of Chicago | Inhibitors and disassemblers of fibrillogenesis |
| MY144532A (en) * | 2001-08-20 | 2011-09-30 | Lundbeck & Co As H | Novel method for down-regulation of amyloid |
| EP1572894B1 (en) * | 2001-11-21 | 2016-04-13 | New York University | Synthetic immunogenic but non-deposit-forming polypeptides and peptides homologous to amyloid beta, prion protein, amylin, alpha synuclein, or polyglutamine repeats for induction of an immune response thereto |
| MY139983A (en) * | 2002-03-12 | 2009-11-30 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
| AU2003256578A1 (en) * | 2002-07-17 | 2004-02-02 | Intellect Neurosciences, Inc. | Peptides and methods of screening immunogenic peptide vaccines against alzheimer's disease |
| EP1560850A2 (en) * | 2002-11-14 | 2005-08-10 | Adherex Technologies, Inc. | Compounds and methods for modulating desmosomal and atypical cadherin-mediated cell adhesion |
| WO2004056318A2 (en) | 2002-12-19 | 2004-07-08 | New York University | Method for treating amyloid disease |
| DE10303974A1 (de) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
| GB0310270D0 (en) * | 2003-05-03 | 2003-06-11 | Univ Edinburgh | Biomolecular devices |
| TWI374893B (en) | 2003-05-30 | 2012-10-21 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
| AR047062A1 (es) | 2003-12-17 | 2006-01-04 | Wyeth Corp | Conjugados portadores de peptidos inmunogenicos a beta y metodos para producirlos |
| SE0401601D0 (sv) | 2004-06-21 | 2004-06-21 | Bioarctic Neuroscience Ab | Protofibril specific antibodies and uses thereof |
| BRPI0516279A (pt) * | 2004-10-06 | 2008-09-02 | Hiroshi Mori | proteìna amilóide variante humana, peptìdeo, gene humano, mrna. cdna sintetizado, anticorpo, método de diagnóstico de doenças amilóides, método para classificação de um componente do agente terapêutico para as doenças amilóides, e fármaco anti-doença amilóide |
| EP1838349A1 (en) * | 2004-12-15 | 2007-10-03 | Neuralab, Ltd. | Amyloid beta antibodies for use in improving cognition |
| TW200635607A (en) * | 2004-12-15 | 2006-10-16 | Elan Pharm Inc | Humanized Aβ antibodies for use in improving cognition |
| WO2006066049A2 (en) | 2004-12-15 | 2006-06-22 | Neuralab Limited | Humanized antibodies that recognize beta amyloid peptide |
| CA2607004C (en) | 2005-05-05 | 2016-01-26 | Sensient Flavors Inc. | Production of beta-glucans and mannans |
| CN117903302A (zh) | 2005-11-30 | 2024-04-19 | Abbvie 公司 | 抗-Aβ球聚体抗体，其相关产品，生产所述抗体的方法，所述抗体的应用以及使用方法 |
| PT1976877E (pt) * | 2005-11-30 | 2014-04-29 | Abbvie Inc | Anticorpos monoclonais contra proteína beta-amilóide e suas utilizações |
| RU2429244C2 (ru) | 2006-03-23 | 2011-09-20 | Байоарктик Ньюросайенс Аб | Улучшенные селективные в отношении протофибрилл антитела и их применение |
| US8784810B2 (en) * | 2006-04-18 | 2014-07-22 | Janssen Alzheimer Immunotherapy | Treatment of amyloidogenic diseases |
| US20090123488A1 (en) * | 2006-08-14 | 2009-05-14 | Thymon, Llc | Compositions and methods for the treatment and prophylaxis of Alzheimer's disease |
| WO2008021295A2 (en) * | 2006-08-14 | 2008-02-21 | Thymon, L.L.C. | Compositions and methods for the treatment and prophylaxis of multiple strains and subtypes of hiv-1 |
| WO2008070284A2 (en) | 2006-10-16 | 2008-06-12 | Johnnie B. Byrd, Sr. Alzheimer's Center And Research Institute | Amyloid beta peptides and methods of uses thereof |
| US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
| TW200902063A (en) | 2007-02-15 | 2009-01-16 | Univ Kumamoto | Therapeutic agent comprising antibody capable of specifically binding to human hmgb-1 as active ingredient |
| EP2123298A4 (en) * | 2007-02-15 | 2011-09-28 | Univ Fukuoka | AGENT FOR SUPPRESSING REJECTION IN AN ORGAN TRANSPLANT COMPRISING ANTI-HMGB-1 ANTIBODY |
| JP5241518B2 (ja) * | 2007-02-15 | 2013-07-17 | 国立大学法人九州大学 | 抗ｈｍｇｂ−１抗体を含む間質性肺疾患治療剤 |
| US20100311767A1 (en) * | 2007-02-27 | 2010-12-09 | Abbott Gmbh & Co. Kg | Method for the treatment of amyloidoses |
| WO2008106657A2 (en) * | 2007-03-01 | 2008-09-04 | Intezyne Technologies, Inc. | Encapsulated amyloid-beta peptides |
| US8003097B2 (en) * | 2007-04-18 | 2011-08-23 | Janssen Alzheimer Immunotherapy | Treatment of cerebral amyloid angiopathy |
| CN101970000A (zh) * | 2007-04-18 | 2011-02-09 | 杨森阿尔茨海默氏症免疫治疗公司 | 脑淀粉样血管病的预防和治疗 |
| DK2182983T3 (da) | 2007-07-27 | 2014-07-14 | Janssen Alzheimer Immunotherap | Behandling af amyloidogene sygdomme med humaniserede anti-abeta antistoffer |
| JO3076B1 (ar) * | 2007-10-17 | 2017-03-15 | Janssen Alzheimer Immunotherap | نظم العلاج المناعي المعتمد على حالة apoe |
| KR101581733B1 (ko) | 2007-11-16 | 2015-12-31 | 더 락커펠러 유니버시티 | 원섬유 형태의 베타아밀로이드 단백질에 대해 특이적인 항체 |
| AU2009266552B2 (en) * | 2008-07-01 | 2014-01-23 | De Staat Der Nederlanden, Vert. Door De Minister Van Vws | Vaccine against amyloid folding intermediate |
| US9067981B1 (en) | 2008-10-30 | 2015-06-30 | Janssen Sciences Ireland Uc | Hybrid amyloid-beta antibodies |
| TWI508976B (zh) * | 2009-04-21 | 2015-11-21 | Univ Rockefeller | 對β－類澱粉蛋白之基原纖維形式具專一性之抗體 |
| US8409584B2 (en) | 2009-05-05 | 2013-04-02 | New York University | Immunotherapy targeting of the shared abnormal conformational state of amyloidogenic peptides/proteins |
| US8748386B2 (en) | 2009-06-10 | 2014-06-10 | New York University | Immunological targeting of pathological Tau proteins |
| CN101920008B (zh) * | 2009-06-15 | 2013-07-31 | 浙江仙琚制药股份有限公司 | 包含Aβ40多肽和铝佐剂的制剂以及纯化Aβ40多肽的方法 |
| CN104744591B (zh) | 2010-04-15 | 2022-09-27 | Abbvie德国有限责任两合公司 | β淀粉样蛋白结合蛋白 |
| EP3533803B1 (en) | 2010-08-14 | 2021-10-27 | AbbVie Inc. | Anti-amyloid-beta antibodies |
| US9926353B2 (en) | 2011-07-19 | 2018-03-27 | New York University | Immunotherapeutic modulation of amyloidogenic disease using non-fibrillogenic, non-amyloidogenic polymerized proteins and peptides |
| US8906382B2 (en) | 2011-07-19 | 2014-12-09 | New York University | Method for treating amyloid disease |
| RS61717B1 (sr) | 2014-07-10 | 2021-05-31 | Bioarctic Ab | Poboljšana antitela koja vezuju a-beta protofibril |
| WO2018038973A1 (en) * | 2016-08-20 | 2018-03-01 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Neuroprotective beta amyloid core peptides and peptidomimetic derivatives |
| CN119136838A (zh) | 2022-02-28 | 2024-12-13 | 特瑞德姆生物科技有限责任两合公司 | 由至少一种β-葡聚糖或甘露聚糖组成或包含至少一种β-葡聚糖或甘露聚糖的偶联物 |
| MX2024010450A (es) | 2022-02-28 | 2024-09-18 | Tridem Bioscience Gmbh & Co Kg | Conjugado que consiste de o que comprende al menos un beta-glucano o un manano. |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0760676B1 (en) | 1994-05-25 | 2001-07-11 | McMICHAEL, John | Materials and methods for treatment of plaquing diseases |
| US5688651A (en) * | 1994-12-16 | 1997-11-18 | Ramot University Authority For Applied Research And Development Ltd. | Prevention of protein aggregation |
| US5948763A (en) * | 1995-06-07 | 1999-09-07 | New York University | Peptides and pharmaceutical compositions thereof for treatment of disorders or diseases associated with abnormal protein folding into amyloid or amyloid-like deposits |
| TWI239847B (en) * | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
| US6787523B1 (en) * | 1997-12-02 | 2004-09-07 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
| US7964192B1 (en) * | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
| AU742970C (en) * | 1997-12-03 | 2003-03-20 | Janssen Alzheimer Immunotherapy | Method of suppressing beta-amyloid-related changes in Alzheimer's disease |
-
2001
- 2001-05-22 AT AT01941526T patent/ATE286072T1/de not_active IP Right Cessation
- 2001-05-22 WO PCT/US2001/016322 patent/WO2001090182A2/en not_active Ceased
- 2001-05-22 IL IL15262501A patent/IL152625A0/xx unknown
- 2001-05-22 CN CNB018100058A patent/CN1249085C/zh not_active Expired - Fee Related
- 2001-05-22 DE DE60108111T patent/DE60108111T2/de not_active Expired - Lifetime
- 2001-05-22 ES ES01941526T patent/ES2238049T3/es not_active Expired - Lifetime
- 2001-05-22 CA CA002408925A patent/CA2408925A1/en not_active Abandoned
- 2001-05-22 AU AU2001274873A patent/AU2001274873B2/en not_active Ceased
- 2001-05-22 JP JP2001586993A patent/JP2003534351A/ja not_active Withdrawn
- 2001-05-22 US US09/861,847 patent/US6713450B2/en not_active Expired - Lifetime
- 2001-05-22 AU AU7487301A patent/AU7487301A/xx active Pending
- 2001-05-22 EP EP01941526A patent/EP1284998B1/en not_active Expired - Lifetime
- 2001-05-22 NZ NZ521939A patent/NZ521939A/en unknown
- 2001-05-22 PT PT01941526T patent/PT1284998E/pt unknown
-
2002
- 2002-10-04 ZA ZA200207992A patent/ZA200207992B/xx unknown
- 2002-11-03 IL IL152625A patent/IL152625A/en not_active IP Right Cessation
-
2003
- 2003-09-19 US US10/666,423 patent/US7427655B2/en not_active Expired - Fee Related
-
2008
- 2008-09-19 US US12/234,456 patent/US7700107B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1444598A (zh) | 2003-09-24 |
| US20020077288A1 (en) | 2002-06-20 |
| US20040043935A1 (en) | 2004-03-04 |
| EP1284998B1 (en) | 2004-12-29 |
| WO2001090182A3 (en) | 2002-05-23 |
| US6713450B2 (en) | 2004-03-30 |
| US20090081204A1 (en) | 2009-03-26 |
| AU2001274873B2 (en) | 2006-10-05 |
| ATE286072T1 (de) | 2005-01-15 |
| IL152625A (en) | 2009-12-24 |
| ZA200207992B (en) | 2003-07-02 |
| DE60108111D1 (de) | 2005-02-03 |
| WO2001090182A2 (en) | 2001-11-29 |
| ES2238049T3 (es) | 2005-08-16 |
| US7700107B2 (en) | 2010-04-20 |
| AU7487301A (en) | 2001-12-03 |
| PT1284998E (pt) | 2005-06-30 |
| CN1249085C (zh) | 2006-04-05 |
| JP2003534351A (ja) | 2003-11-18 |
| US7427655B2 (en) | 2008-09-23 |
| DE60108111T2 (de) | 2005-12-08 |
| NZ521939A (en) | 2004-04-30 |
| EP1284998A2 (en) | 2003-02-26 |
| IL152625A0 (en) | 2003-06-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2001274873B2 (en) | Synthetic immunogenic but non-amyloidogenic peptides homologous to amyloid beta for induction of an immune response to amyloid beta and amyloid deposits | |
| AU2001274873A1 (en) | Synthetic immunogenic but non-amyloidogenic peptides homologous to amyloid beta for induction of an immune response to amyloid beta and amyloid deposits | |
| EP1572894B1 (en) | Synthetic immunogenic but non-deposit-forming polypeptides and peptides homologous to amyloid beta, prion protein, amylin, alpha synuclein, or polyglutamine repeats for induction of an immune response thereto | |
| US9102752B2 (en) | Peptide vaccine for prevention and immunotherapy of dementia of the Alzheimer's type | |
| JP5717210B2 (ja) | 免疫化組成物およびアミロイド前駆体タンパク質のβ−セクレターゼ切断部位に対する免疫応答を誘発するための方法 | |
| CN101420983B (zh) | 包含超分子抗原构建体的组合物和方法 | |
| EP2330113B1 (en) | Immunological methods and compositions for the treatment of Alzheimer's disease | |
| KR20080097188A (ko) | 항아밀로이드 면역성성분, 그 제조방법 및 용도 | |
| WO2010011999A2 (en) | Methods and compositions for eliciting an amyloid-selective immune response | |
| CA2450783A1 (en) | Multiple antigenic peptide displaying multiple copies of an epitope of plaque-forming polypeptide and methods of using same | |
| WO2021163239A1 (en) | Peptide immunogens targeting islet amyloid polypeptide (iapp) for prevention and treatment of disorders related to aggregated iapp | |
| US20220023401A1 (en) | Peptide vaccine for prevention and immunotherapy of dementia of the alzheimer's type | |
| HUE025186T2 (en) | Methods and methods using supramolecular constructs | |
| HK1158665B (en) | Immunological methods and compositions for the treatment of alzheimer's disease |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |