Analysis of pathological mechanism of Spinocerebellar Ataxia type 6 (SCA6) by chemical biology.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16484
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Shin Minkyoung 東京医科歯科大学, 難治疾患研究所, プロジェクト助教 (60738566)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 脊髄小脳失調症６型 / SCA6 / 新規オートファジー

Outline of Final Research Achievements

In this study, we examined whether the expression of Cav2.1-polyQ and α1ACT-polyQ, the causative gene products of spinocerebellar ataxia type 6 (SCA6) are regulated by autophagy. Cells were transfected with Cav2.1-polyQ and α1ACT-polyQ and we could identify both of polyQ protein expression were reduced by autophagy inducer, TMD-6. Moreover, after administration of TMD-6 to SCA6 mice, polyglutamine symptoms have been confirmed to be relieved. These observations suggest that polyQ protein expression in SCA6 and SCA6-associated pathological features were reduced by autophagy.

Free Research Field

病態細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究結果より、SCA6原因遺伝子産物であるCav2.1-polyQおよびα1ACT-polyQの両polyQタンパク質がオートファジー誘導により減少することが明らかになった。この結果から、これまで治療法の確立されていないSCA6に対してオートファジー誘導が有効であり、治療薬開発に応用できると考えられる。