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2021 Fiscal Year Final Research Report

Comprehensive analysis of aggregate-resistant structure and its application for disease prevention

Research Project

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Project/Area Number 20K21585
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 52:General internal medicine and related fields
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Hoshino Atsushi  京都府立医科大学, 医学(系)研究科(研究院), 助教 (50737210)

Co-Investigator(Kenkyū-buntansha) 渡邊 義久  京都府立医科大学, 医学(系)研究科(研究院), 講師 (50363990)
Project Period (FY) 2020-07-30 – 2022-03-31
Keywordsパーキンソン病 / αシヌクレイン / 凝集抵抗性 / ゲノム編集
Outline of Final Research Achievements

Comprehensive analysis of aggregation property in α-synuclein protein was conducted using all single amino acid substitution library. Among aggregation-resistant single substitutions, the XXX substitution has been reported as human SNP and is evolutionarily conserved in many species. The XXX knock-in mouse was generated and underwent fibril seed injection in striatum as Parkinson’s disease model. Fibril transmission was observed in the control wild-type mice. In contrast, the knock-in mice exhibited the clear disappearance of α-synuclein fibril. These results indicate that XXX is disease-protective polymorphism can be applied to disease prevention by genome editing in the future.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究ではパーキンソン病に保護的にはたらく、安全な遺伝子変異を同定することに成功した。この遺伝子変異はパーキンソン病の原因物質であるαシヌクレインの凝集を抑制するもので、既にヒトでの保有が確認され、一部の生物でも保存されているので安全な遺伝に変異と考えられる。今後はこの遺伝子変異を最近発展が目覚ましいゲノム編集技術で導入することができれば画期的なパーキンソン病予防方法が確立されることが期待されます。

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Published: 2023-01-30  

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