JP4223681B2 - 病原性タンパク質沈着の基礎構造の会合の測定方法 - Google Patents
病原性タンパク質沈着の基礎構造の会合の測定方法 Download PDFInfo
- Publication number
- JP4223681B2 JP4223681B2 JP2000513150A JP2000513150A JP4223681B2 JP 4223681 B2 JP4223681 B2 JP 4223681B2 JP 2000513150 A JP2000513150 A JP 2000513150A JP 2000513150 A JP2000513150 A JP 2000513150A JP 4223681 B2 JP4223681 B2 JP 4223681B2
- Authority
- JP
- Japan
- Prior art keywords
- probe
- pathogenic protein
- pathogenic
- protein
- association
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 105
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 105
- 238000000034 method Methods 0.000 title claims abstract description 54
- 230000008021 deposition Effects 0.000 title claims abstract description 52
- 230000001717 pathogenic effect Effects 0.000 title claims description 78
- 239000000523 sample Substances 0.000 claims abstract description 77
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 29
- 238000001514 detection method Methods 0.000 claims abstract description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
- 201000010099 disease Diseases 0.000 claims abstract description 18
- 238000004220 aggregation Methods 0.000 claims abstract description 14
- 210000001124 body fluid Anatomy 0.000 claims abstract description 12
- 239000010839 body fluid Substances 0.000 claims abstract description 10
- 239000007791 liquid phase Substances 0.000 claims abstract description 6
- 238000005259 measurement Methods 0.000 claims description 33
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 26
- 238000002060 fluorescence correlation spectroscopy Methods 0.000 claims description 25
- 208000037259 Amyloid Plaque Diseases 0.000 claims description 15
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 15
- 210000001519 tissue Anatomy 0.000 claims description 9
- 210000004556 brain Anatomy 0.000 claims description 8
- 239000002245 particle Substances 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 6
- 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 claims description 4
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 claims description 4
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 claims description 4
- 206010002022 amyloidosis Diseases 0.000 claims description 4
- 239000012530 fluid Substances 0.000 claims description 4
- 239000012634 fragment Substances 0.000 claims description 4
- 239000000178 monomer Substances 0.000 claims description 4
- 230000004770 neurodegeneration Effects 0.000 claims description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 4
- 102000004190 Enzymes Human genes 0.000 claims description 3
- 108090000790 Enzymes Proteins 0.000 claims description 3
- 208000024777 Prion disease Diseases 0.000 claims description 3
- 238000002795 fluorescence method Methods 0.000 claims description 3
- 238000001506 fluorescence spectroscopy Methods 0.000 claims description 3
- 238000004020 luminiscence type Methods 0.000 claims description 3
- 210000000653 nervous system Anatomy 0.000 claims description 3
- 230000003287 optical effect Effects 0.000 claims description 3
- 238000000053 physical method Methods 0.000 claims description 3
- 230000028327 secretion Effects 0.000 claims description 3
- 108090001008 Avidin Proteins 0.000 claims description 2
- 208000023105 Huntington disease Diseases 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 108091005804 Peptidases Proteins 0.000 claims description 2
- 239000004365 Protease Substances 0.000 claims description 2
- 229960002685 biotin Drugs 0.000 claims description 2
- 235000020958 biotin Nutrition 0.000 claims description 2
- 239000011616 biotin Substances 0.000 claims description 2
- 239000008280 blood Substances 0.000 claims description 2
- 210000004369 blood Anatomy 0.000 claims description 2
- 230000003196 chaotropic effect Effects 0.000 claims description 2
- 238000002983 circular dichroism Methods 0.000 claims description 2
- 239000003599 detergent Substances 0.000 claims description 2
- 210000003296 saliva Anatomy 0.000 claims description 2
- 238000004611 spectroscopical analysis Methods 0.000 claims description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 2
- 238000002604 ultrasonography Methods 0.000 claims description 2
- 210000002700 urine Anatomy 0.000 claims description 2
- 208000005531 Immunoglobulin Light-chain Amyloidosis Diseases 0.000 claims 2
- 208000022256 primary systemic amyloidosis Diseases 0.000 claims 2
- 208000023769 AA amyloidosis Diseases 0.000 claims 1
- 208000023761 AL amyloidosis Diseases 0.000 claims 1
- 206010059245 Angiopathy Diseases 0.000 claims 1
- 206010010356 Congenital anomaly Diseases 0.000 claims 1
- 208000034846 Familial Amyloid Neuropathies Diseases 0.000 claims 1
- 206010016202 Familial Amyloidosis Diseases 0.000 claims 1
- 206010019889 Hereditary neuropathic amyloidosis Diseases 0.000 claims 1
- 208000037196 Medullary thyroid carcinoma Diseases 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 1
- 102000015736 beta 2-Microglobulin Human genes 0.000 claims 1
- 108010081355 beta 2-Microglobulin Proteins 0.000 claims 1
- 230000031700 light absorption Effects 0.000 claims 1
- 210000004880 lymph fluid Anatomy 0.000 claims 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 claims 1
- 230000002981 neuropathic effect Effects 0.000 claims 1
- 230000005855 radiation Effects 0.000 claims 1
- 230000003248 secreting effect Effects 0.000 claims 1
- 208000013818 thyroid gland medullary carcinoma Diseases 0.000 claims 1
- 201000007905 transthyretin amyloidosis Diseases 0.000 claims 1
- 238000000151 deposition Methods 0.000 abstract description 41
- 230000001575 pathological effect Effects 0.000 abstract 9
- 235000018102 proteins Nutrition 0.000 description 77
- 108091000054 Prion Proteins 0.000 description 45
- 102000029797 Prion Human genes 0.000 description 45
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 22
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 22
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 20
- 239000012064 sodium phosphate buffer Substances 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 11
- 235000001014 amino acid Nutrition 0.000 description 10
- 238000002372 labelling Methods 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 208000018756 Variant Creutzfeldt-Jakob disease Diseases 0.000 description 8
- 230000002776 aggregation Effects 0.000 description 8
- 229940024606 amino acid Drugs 0.000 description 8
- 208000005881 bovine spongiform encephalopathy Diseases 0.000 description 8
- 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 8
- 208000015181 infectious disease Diseases 0.000 description 8
- 230000002458 infectious effect Effects 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 150000001413 amino acids Chemical group 0.000 description 7
- 238000009792 diffusion process Methods 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- -1 or vice versa Chemical compound 0.000 description 7
- 239000013543 active substance Substances 0.000 description 6
- 239000007850 fluorescent dye Substances 0.000 description 6
- 208000008864 scrapie Diseases 0.000 description 6
- 238000003745 diagnosis Methods 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 230000035945 sensitivity Effects 0.000 description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 229940009098 aspartate Drugs 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229930195712 glutamate Natural products 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 239000004474 valine Substances 0.000 description 4
- 102000001049 Amyloid Human genes 0.000 description 3
- 108010094108 Amyloid Proteins 0.000 description 3
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 3
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 3
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 3
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 241000699673 Mesocricetus auratus Species 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 229960001230 asparagine Drugs 0.000 description 3
- 235000009582 asparagine Nutrition 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000002405 diagnostic procedure Methods 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 229960000310 isoleucine Drugs 0.000 description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- 108010057077 prion protein (90-231) Proteins 0.000 description 3
- 238000011895 specific detection Methods 0.000 description 3
- 102000013498 tau Proteins Human genes 0.000 description 3
- 108010026424 tau Proteins Proteins 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 230000003941 amyloidogenesis Effects 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000001215 fluorescent labelling Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000006911 nucleation Effects 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000000527 sonication Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- VGIRNWJSIRVFRT-UHFFFAOYSA-N 2',7'-difluorofluorescein Chemical compound OC(=O)C1=CC=CC=C1C1=C2C=C(F)C(=O)C=C2OC2=CC(O)=C(F)C=C21 VGIRNWJSIRVFRT-UHFFFAOYSA-N 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- IMYZQPCYWPFTAG-UHFFFAOYSA-N Mecamylamine Chemical compound C1CC2C(C)(C)C(NC)(C)C1C2 IMYZQPCYWPFTAG-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 1
- 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 1
- 239000004760 aramid Substances 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 229920003235 aromatic polyamide Polymers 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000012459 cleaning agent Substances 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000005314 correlation function Methods 0.000 description 1
- 238000011157 data evaluation Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000009593 lumbar puncture Methods 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 230000001722 neurochemical effect Effects 0.000 description 1
- 230000000508 neurotrophic effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000002331 protein detection Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000010517 secondary reaction Methods 0.000 description 1
- 238000011896 sensitive detection Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 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 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000012546 transfer Methods 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
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Chemical & Material Sciences (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19741486 | 1997-09-19 | ||
| DE19741486.9 | 1997-09-19 | ||
| DE19752712.4 | 1997-11-28 | ||
| DE1997152712 DE19752712C2 (de) | 1997-11-28 | 1997-11-28 | Verfahren zur Messung der Assoziation von Teilstrukturen pathologischer Proteinablagerungen |
| DE19818917.6 | 1998-04-28 | ||
| DE19818917 | 1998-04-28 | ||
| PCT/EP1998/005958 WO1999015903A1 (de) | 1997-09-19 | 1998-09-18 | Verfahren zur messung der assoziation von teilstrukturen pathologischer proteinablagerungen |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2001517800A JP2001517800A (ja) | 2001-10-09 |
| JP2001517800A5 JP2001517800A5 (enExample) | 2006-12-07 |
| JP4223681B2 true JP4223681B2 (ja) | 2009-02-12 |
Family
ID=27217757
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000513150A Expired - Lifetime JP4223681B2 (ja) | 1997-09-19 | 1998-09-18 | 病原性タンパク質沈着の基礎構造の会合の測定方法 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US6498017B2 (enExample) |
| EP (1) | EP1015888B1 (enExample) |
| JP (1) | JP4223681B2 (enExample) |
| AT (1) | ATE223058T1 (enExample) |
| AU (1) | AU9541398A (enExample) |
| DE (1) | DE59805338D1 (enExample) |
| WO (1) | WO1999015903A1 (enExample) |
Families Citing this family (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001023894A1 (de) * | 1999-09-28 | 2001-04-05 | Evotec Oai Ag | Quantitative analyse und typisierung subzellulärer partikel |
| DE19952955A1 (de) | 1999-11-03 | 2001-05-17 | Acgt Progenomics Ag | Verfahren zur Charakterisierung und zur Auftrennung von molekularen Assoziaten |
| DE10013854A1 (de) * | 2000-03-17 | 2001-09-20 | Zeiss Carl Jena Gmbh | Anordnung und Verfahren zur Untersuchung von Wirkstoffen zur Beeinflussung intrazellulärer Vorgänge |
| WO2003090599A2 (en) * | 2002-04-25 | 2003-11-06 | Brainsgate Ltd. | Methods and apparatus for modifying properties of the bbb and cerebral circulation by using the neuroexcitatory and/or neuroinhibitory effects of odorants on nerves in the head |
| US7640062B2 (en) | 2000-05-08 | 2009-12-29 | Brainsgate Ltd. | Methods and systems for management of alzheimer's disease |
| US7146209B2 (en) * | 2000-05-08 | 2006-12-05 | Brainsgate, Ltd. | Stimulation for treating eye pathologies |
| US6603546B1 (en) * | 2000-07-21 | 2003-08-05 | I.S.S. (Usa) Inc. | Rapid high throughput spectrometer and method |
| US20050026165A1 (en) * | 2001-05-31 | 2005-02-03 | Cindy Orser | Detection of conformationally altered proteins and prions |
| MXPA03011000A (es) | 2001-05-31 | 2004-02-27 | Arete Associates | Metodo de sensor de proteinas deformadas. |
| EP1321771A1 (de) * | 2001-12-21 | 2003-06-25 | Evotec Analytical Systems GmbH | Verfahren zur qualitativen und/oder quantitativen Bestimmung von Aggregaten |
| EP1572937B1 (en) * | 2002-04-09 | 2012-02-08 | The Scripps Research Institute | Motif-grafted hybrid polypeptides and uses thereof |
| WO2004043218A2 (en) * | 2002-11-14 | 2004-05-27 | Brainsgate Ltd. | Surgical tools and techniques for stimulation |
| US7684859B2 (en) * | 2002-04-25 | 2010-03-23 | Brainsgate Ltd. | Stimulation of the OTIC ganglion for treating medical conditions |
| WO2005008212A2 (en) * | 2003-06-20 | 2005-01-27 | The Regents Of The University Of California | Modulated excitation fluorescence analysis |
| US20060035242A1 (en) * | 2004-08-13 | 2006-02-16 | Michelitsch Melissa D | Prion-specific peptide reagents |
| EP1600774A1 (de) * | 2004-03-12 | 2005-11-30 | Ludwig-Maximilians-Universität München | Verfahren zur Identifizierung von Substanzen zur Beeinflussung der Aggregationen von Proteinen |
| US9233245B2 (en) | 2004-02-20 | 2016-01-12 | Brainsgate Ltd. | SPG stimulation |
| US8055347B2 (en) | 2005-08-19 | 2011-11-08 | Brainsgate Ltd. | Stimulation for treating brain events and other conditions |
| US8010189B2 (en) * | 2004-02-20 | 2011-08-30 | Brainsgate Ltd. | SPG stimulation for treating complications of subarachnoid hemorrhage |
| JP4338590B2 (ja) | 2004-06-03 | 2009-10-07 | 独立行政法人科学技術振興機構 | 蛍光相関分光法による抗原の迅速検出及び/又は測定法。 |
| US20090299418A1 (en) * | 2004-08-23 | 2009-12-03 | Brainsgate Ltd. | Concurrent bilateral spg modulation |
| US20060057671A1 (en) * | 2004-09-10 | 2006-03-16 | Orser Cindy S | Immobilized probes and methods of detecting conformationally altered prion proteins |
| WO2006076683A2 (en) * | 2005-01-13 | 2006-07-20 | Novartis Vaccines And Diagnostics Inc. | Isolation and detection of pathogenic prions |
| CA2594840A1 (en) * | 2005-01-13 | 2006-07-20 | Novartis Vaccines And Diagnostics Inc. | Elisa assays using prion-specific peptide reagents |
| CA2597912C (en) * | 2005-02-15 | 2013-06-04 | Adlyfe, Inc. | Method for detecting misfolded proteins and prions |
| US20090253217A1 (en) | 2005-09-12 | 2009-10-08 | Japan Science And Technology Agency | Method of Quickly Detecting Antigen Using Fluorescence Correlation Spectroscopy or Fluorescence Cross-Correlation Spectroscopy |
| ES2323725T3 (es) * | 2006-07-28 | 2009-07-23 | Vista Ventures Gmbh | Procedimiento para la deteccion de oligomeros de amiloide beta en fluidos corporales. |
| MX2009001079A (es) * | 2006-07-28 | 2009-02-10 | Adlyfe Inc | Sondas de peptido para diagnosis y terapeutica. |
| WO2008022035A2 (en) * | 2006-08-10 | 2008-02-21 | The Scripps Research Institute | Methods for identifying cellular modulators of disaggregation activity or aggregation activity in an animal |
| US20090210026A1 (en) * | 2006-08-17 | 2009-08-20 | Brainsgate Ltd. | Spg stimulation for enhancing neurogenesis and brain metabolism |
| JP2010043865A (ja) * | 2006-12-12 | 2010-02-25 | Olympus Corp | 異常型プリオンの検出方法 |
| US7860569B2 (en) | 2007-10-18 | 2010-12-28 | Brainsgate, Ltd. | Long-term SPG stimulation therapy for prevention of vascular dementia |
| CN102083450A (zh) * | 2008-04-30 | 2011-06-01 | 诺华有限公司 | 致病性构象异构体的分析 |
| US20110174064A1 (en) * | 2008-10-02 | 2011-07-21 | Ramot At Tel-Aviv University Ltd. | Method and system for emitting light |
| US20100129290A1 (en) * | 2008-11-26 | 2010-05-27 | I.S.T. Corporation | Smart contrast agent and detection method for detecting transition metal ions |
| US20100227794A1 (en) * | 2008-11-26 | 2010-09-09 | I.S.T. Corporation | Smart contrast agent and method for detecting transition metal ions and treating related disorders |
| US10512794B2 (en) | 2016-12-16 | 2019-12-24 | Brainsonix Corporation | Stereotactic frame |
| US9061133B2 (en) | 2012-12-27 | 2015-06-23 | Brainsonix Corporation | Focused ultrasonic transducer navigation system |
| US10974078B2 (en) | 2012-12-27 | 2021-04-13 | Brainsonix Corporation | Treating degenerative dementia with low intensity focused ultrasound pulsation (LIFUP) device |
| US9675796B2 (en) | 2013-11-10 | 2017-06-13 | Brainsgate Ltd. | Implant and delivery system for neural stimulator |
| US10271907B2 (en) | 2015-05-13 | 2019-04-30 | Brainsgate Ltd. | Implant and delivery system for neural stimulator |
| AU2017378419A1 (en) * | 2016-12-15 | 2019-07-04 | Brainsonix Corporation | Treating degenerative dementia using low intensity focused ultrasound pulsation (lifup) device |
| GB201805466D0 (en) * | 2018-04-03 | 2018-05-16 | Vukojevic Vladana | Methods |
| US11759661B2 (en) | 2020-05-20 | 2023-09-19 | Brainsonix Corporation | Ultrasonic transducer treatment device |
| US12257446B2 (en) | 2020-08-24 | 2025-03-25 | Brainsonix Corporation | Systems and methods for neuromodulation of neuronal circuits using transcranial focused microwave pulses |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991016628A1 (en) * | 1990-04-24 | 1991-10-31 | The Regents Of The University Of California | Purification, detection and methods of use of protease nexin-2 |
| WO1993023432A1 (en) * | 1992-05-15 | 1993-11-25 | New York University | Soluble prion polypeptides, and methods for detecting and purifying thereof |
| EP1416280A3 (en) | 1995-09-14 | 2005-08-10 | The Regents of the University of California | Antibodies specific for native PrPsc |
| DK0862653T3 (da) * | 1995-10-26 | 2002-03-11 | Ernst Ludwig Prof Winnacker | Nukleinsyremolekyler, som er i stand til at skelne mellem PrPc- og PrPSc-isoformerne af prionproteiner og fremgangsmåder til fremstilling deraf |
-
1998
- 1998-09-18 AU AU95413/98A patent/AU9541398A/en not_active Abandoned
- 1998-09-18 WO PCT/EP1998/005958 patent/WO1999015903A1/de not_active Ceased
- 1998-09-18 US US09/508,959 patent/US6498017B2/en not_active Expired - Lifetime
- 1998-09-18 DE DE59805338T patent/DE59805338D1/de not_active Expired - Lifetime
- 1998-09-18 EP EP98948990A patent/EP1015888B1/de not_active Expired - Lifetime
- 1998-09-18 AT AT98948990T patent/ATE223058T1/de not_active IP Right Cessation
- 1998-09-18 JP JP2000513150A patent/JP4223681B2/ja not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JP2001517800A (ja) | 2001-10-09 |
| ATE223058T1 (de) | 2002-09-15 |
| US20020042121A1 (en) | 2002-04-11 |
| DE59805338D1 (de) | 2002-10-02 |
| EP1015888A1 (de) | 2000-07-05 |
| WO1999015903A1 (de) | 1999-04-01 |
| EP1015888B1 (de) | 2002-08-28 |
| AU9541398A (en) | 1999-04-12 |
| US6498017B2 (en) | 2002-12-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4223681B2 (ja) | 病原性タンパク質沈着の基礎構造の会合の測定方法 | |
| US6245572B1 (en) | Flow cytometric characterization of amyloid fibrils | |
| Bruggink et al. | Methods for analysis of amyloid-β aggregates | |
| JP5009987B2 (ja) | 体液中のアミロイド−βオリゴマーの検出方法 | |
| AU2004297579B2 (en) | Detection of conformationally altered proteins and prions | |
| RU2642314C2 (ru) | Способы избирательной количественной оценки агрегатов а-бета | |
| MXPA02006362A (es) | Metodos para la deteccion de proteinas amiloidogenicas. | |
| US20210109114A1 (en) | Diagnostic method for multiple sclerosis | |
| Funke et al. | Single particle detection of Aβ aggregates associated with Alzheimer’s disease | |
| Sancesario et al. | The load of amyloid-β oligomers is decreased in the cerebrospinal fluid of Alzheimer's disease patients | |
| US20130289140A1 (en) | Biological complex specific for alzheimer's disease detection in vitro and use thereof | |
| JP5904418B2 (ja) | 前頭側頭葉変性の鑑別診断のための生体外の方法 | |
| Kulenkampff et al. | An antibody scanning method for the detection of α-synuclein oligomers in the serum of Parkinson's disease patients | |
| CN112639470A (zh) | 淀粉样物质相关疾病的诊断方法 | |
| Giese et al. | Putting prions into focus: application of single molecule detection to the diagnosis of prion diseases | |
| EP1112500B1 (en) | Tau as a marker for early cns damage | |
| US20230228771A1 (en) | Determination of disease-specific protein aggregates in stool samples | |
| KR20020065504A (ko) | 분자 회합물의 특성화 및 분리 방법 | |
| CN117054664A (zh) | 用于诊断阿尔茨海默病的试剂盒及应用 | |
| CA2656417C (en) | Process for the selective determination of pathological protein deposits | |
| JP4568840B2 (ja) | アルツハイマー病の検査方法 | |
| Kulenkampff et al. | An antibody scanning method for the detection of a-synuclein oligomers in the serum of Parkinson's disease patients | |
| JP2007017348A (ja) | タンパク質凝集の分析方法 | |
| Goto et al. | Plasma acetylated α-synuclein as a novel quantitative biomarker for Parkinson's disease | |
| CN117007819A (zh) | 用于辅助诊断阿尔茨海默病的试剂盒 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20040413 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20040624 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20060418 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20060718 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20060919 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20061018 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20070717 |
|
| RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20071015 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20071019 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20071114 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20071019 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20071211 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080430 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20080513 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20080729 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20081021 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20081118 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20081120 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20111128 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121128 Year of fee payment: 4 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20131128 Year of fee payment: 5 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| EXPY | Cancellation because of completion of term |