2021 Fiscal Year Final Research Report
Association of RNA helicase with mitochondrial damage in ALS
Project/Area Number |
20K22682
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0704:Neuroscience, brain sciences, and related fields
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Research Institution | Shiga University of Medical Science |
Principal Investigator |
Hikiami Ryota 滋賀医科大学, 神経難病研究センター, 客員助教 (10885354)
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Project Period (FY) |
2020-09-11 – 2022-03-31
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Keywords | ALS / FUS / RNA helicase / DHX30 |
Outline of Final Research Achievements |
FUS is one of the causative genes of amyotrophic lateral sclerosis (ALS). In this study, we identified DHX30 as an interacting protein with FUS. DHX30 is an RNA helicase localizing mainly within mitochondria and required for the translation of mitochondrial DNA. It is speculated that DHX30 play an important role in central nervous system, considering previous reports that the missense mutations in the DHX30 gene have been identified as a genetic cause of neurodevelopmental disorders. FUS mutants disrupted the conformation of mitochondrial DHX30 via excessive disulfide formation, leading to its loss of function, mitochondrial dysfunction and neuronal cytotoxicity. Further studies are needed to determine whether restoration of DHX30 function could be a potential therapeutic target.
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Free Research Field |
neuroscience
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Academic Significance and Societal Importance of the Research Achievements |
FUS遺伝子変異は本邦の家族性ALSで2番目に多く、孤発性ALSでは最も多い遺伝子変異で、その一部は若年発症・急速進行性ALSの原因となります。ただその病態機序は不明で、有効な治療法はありません。私達の研究により、ALS-FUSのミトコンドリア障害において、DHX30が鍵分子である可能性が示唆されました。また遺伝子変異のない孤発性ALSでもDHX30が関与している可能性も考慮されました。DHX30の機能回復は、神経難病であるALSの治療ターゲットとして今後の発展性が期待されます。
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