| Project/Area Number |
12460130
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | Obihiro University of Agriculture and Veterinary Medicine |
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Principal Investigator |
MAKINO Sou-ichi (2002) Obihiro University of Agriculture and Veterinary Medicine, Faculty of animal husbandry, Associate Professor, 畜産学部, 助教授 (30181621)
品川 森一 (2000-2001) 帯広畜産大学, 畜産学部, 教授 (00001537)
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| Co-Investigator(Kenkyū-buntansha) |
HORIUCHI Motohiro Obihiro University of Agriculture and Veterinary Medicine, Research Center for protozoan diseases, Associate Professor, 原虫病研究センター, 助教授 (30219216)
FURUOKA Hidefumi Obihiro University of Agriculture and Veterinary Medicine, Faculty of animal husbandry, Associate Professor, 畜産学部, 助教授 (60238665)
牧野 壮一 帯広畜産大学, 畜産学部, 助教授 (30181621)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Keywords | prion / scrapie / PrP / conformational transformation / glycosaminoglycan / synthetic peptide / BSE / 伝達性海綿状脳症 / 種特異性 |
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| Research Abstract |
An abnormal isoform of prion protein (PrPSc) is a major component of the infectious agent "prion" and the biosynthesis of PrPSc play a central role in pathogenesis of prion diseases. Once prion enters the host, PrPSc binds to normal prion protein (PrPC) and converts PrPC into PrPSc. During the conformational transformation, PrPSc acts as a template or seed. In this study, we analyzed inter-molecular interaction between PrPC and PrPSc that is a key event in PrPSc generation.
We found that PrPC bound to heterologous PrPSc but did not convert to PrPSc and that the conversion reaction could be interfered by heterologous PrPC. These finding indicate that the conversion of PrPC to PrPSc is controlled more by the conformational transformation step. Analysis using mutant PrPC revealed that three amino acids locating central part of PrP is major determinant of the conversion reaction. We also examined the micro-environment where the conversion reaction takes place and found that sulfated glycans
… More
, a constituent of glycosaminoglycan, facilitated the PrPSc generation. Glycosaminoglycan is a major component of extracellular matrix so that environment in the outer surface of cells may be involved in the interaction between PrPC and PrPSc. Furthermore we found PrP synthetic peptide, aa119-141, 167-179 and 200-223 inhibited the PrPSc formation. These peptides formed high beta-sheet aggregates and bound to PrPC, implying the PrPC binding domain on the PrPSc molecule. In this study we have succeeded to produce an extensive panel of monoclonal antibodies against PrP molecule. The mAbs in this panel could be divided into at least 11 groups based on their epitope. Seven of them recognized linear epitopes on PrPC and/or denatured PrP molecule, while 3 of them recognized discontinuous epitopes on PrP molecule. The remaining one group of mAb, mAb 6H10 could differentiate PrPSc from PrPC. This extensive panel of mAb will be invaluable for further analyses of interaction between PrPSc and PrPC. Less
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