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2019 Fiscal Year Final Research Report

Study for bringing a new dimension in the pathogenesis of prion disease.

Research Project

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Project/Area Number 17K19540
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Pathology, Infection/Immunology, and related fields
Research InstitutionTohoku University

Principal Investigator

Doh-ura katsumi  東北大学, 医学系研究科, 教授 (00263012)

Project Period (FY) 2017-06-30 – 2020-03-31
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.

Free Research Field

神経化学

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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Published: 2021-02-19  

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