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2020 Fiscal Year Final Research Report

Elucidation of action mechanism of repeat RNA-binding small molecules that improve disease phenotype in spinocerebellar ataxia type 31

Research Project

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Project/Area Number 17K01962
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Chemical biology
Research InstitutionOsaka University

Principal Investigator

Shibata Tomonori  大阪大学, 産業科学研究所, 助教 (80711960)

Project Period (FY) 2017-04-01 – 2021-03-31
Keywords脊髄小脳変性症31型 / UGGAAリピート / RNA結合性低分子
Outline of Final Research Achievements

This study is aimed to elucidate the action mechanism of small molecules that alleviate disease phenotype in spinocerebellar ataxia type 31 (SCA31) model. In this study, we found naphthyridine carbamate dimer (NCD) as small molecules targeting UGGAA repeat in SCA31. NCD inhibited the interaction of UGGAA repeats with RNA-binding proteins and the formation of nuclear RNA foci consisting of UGGAA repeat. We demonstrated that NCD alleviated UGGAA repeat-mediated RNA toxicity in SCA31 Drosophila model, suggesting that targeting UGGAA repeat by small molecules have a potential for treatment of SCA31.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

脊髄小脳失調症31型(SCA31)は、TGGAAリピートが原因で発症する難治性疾患であり、TGGAAリピートから転写されるUGGAAリピートが関与するRNA介在性神経疾患である。現時点ではSCA31を完治する方法はなく、症状改善に資する治療法開発が待たれている。
本研究成果により、UGGAAリピート結合分子によるリピートRNAの機能制御及びSCA31モデルショウジョウバエにおける治療効果が実証され、これらの分子ツールを用いた発症機構の分子レベルでの解明や治療法開発の進展などが期待できる。

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Published: 2022-01-27  

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