Study for bringing a new dimension in the pathogenesis of prion disease.
Project/Area Number |
17K19540
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Research Field |
Pathology, Infection/Immunology, and related fields
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Research Institution | Tohoku University |
Principal Investigator |
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Project Period (FY) |
2017-06-30 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | プリオン / 脳神経疾患 / 病因論 |
Outline of Final Research Achievements |
Intracerebral inoculation of hamster-adapted prions into the brain of mice lacking the cellular prion protein (PrPc) results in non-inflammatory brain lesions. In this study we investigated how this phenomenon is associated with prions, and we reconsidered the pathogenesis of prion disease. The brain homogenate of PrPc-deficient mice infected with hamster-adapted prions was inoculated into the brain of new PrPc-deficient mice, and the mice were observed for about 3 years. The results indicated that there was neither neurodegeneration nor abnormal protein deposition in the brain. Thus, hamster-adapted prions themselves caused damage in the brain of PrPc-deficient mice, but their pathogenicity did not propagate without PrPc. These findings suggest that pathogenicity can be separated from prion transmission; PrPc is required for the transmission of prions, but there is a PrPc-free pathway in the pathogenesis of prions.
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Academic Significance and Societal Importance of the Research Achievements |
ノーベル賞受賞者であるプルシナー博士が提唱したプリオン説は、世界中の研究者のコンセンサスを得て定着しているが、一部には未だにプリオン説で説明し難い現象が存在する。例えば、特定の凝集プリオン蛋白でのみ伝播性・病原性が観察され、伝播性・病原性が観察されない凝集プリオン蛋白が大半である。また、異常型プリオン蛋白の存在を実証できないプリオン病が存在する。今回、申請者の発見を展開した本研究の成果である「プリオンの伝播と病原性は分離できる」は、プリオン病の病因論に新局面をもたらすことが期待される。また、この成果はアルファ・シヌクレイノパチーなどプリオン病類縁疾患の病因論にも影響を与える可能性がある。
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Report
(4 results)
Research Products
(22 results)