| Project/Area Number |
11680731
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Tohoku University |
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Principal Investigator |
MURAMOTO Tamaki Tohoku University, school of Medicine, Research Associate, 大学院・医学系研究科, 助手 (40302096)
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| Co-Investigator(Kenkyū-buntansha) |
KITAMOTO Tetsuyuki Tohoku University, school of Medicine, Professor, 大学院・医学系研究科, 教授 (20192560)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | prion / conformation / mutation / bioassay / gene therapy / amyloid / neuronal degeneration / transgenic mice |
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| Research Abstract |
Prions, the causative agents of prion diseases, are mainly composed of the infectious form of prion protein (PrPSc). The main event of prion proliferation is the conformational change of the cellular form of prion protein (PrPC), a normal component of neurons, into the infectious form through PrPC-PrPSc interaction. The mechanism of this isoform conversion of prion protein (PrP) remains enigmatic.
In order to solve this issue, we determined the domains of PrP that are essential for the isoform conversion. In addition, we discovered unique phenomena caused by deletion mutants of PrP. Some mutant PrPs with one of the essential domains deleted inhibited the isoform conversion of wild type PrP while the other deletion mutant markedly enhanced PrP amyloid deposition when mice co-expressing the wild type and mutant PrPs are inoculated with prions. These data not only provide insights about the mechanism of prion and amyloid formation by PrP but also initiate new studies toward the development of methods to treat or prevent prion diseases using mutant PrPs.
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