2021 Fiscal Year Final Research Report
Development of a novel therapeutics for muscular dystrophy by targeting mitophagy.
| Project/Area Number |
19K07102
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47040:Pharmacology-related
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
堀尾 嘉幸 札幌医科大学, 医学部, 教授 (30181530)
久野 篤史 札幌医科大学, 医学部, 准教授 (30468079)
岩原 直敏 札幌医科大学, 医学部, 助教 (00613085)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 筋ジストロフィー / マイトファジー / オートファジー / SIRT1 / ミトコンドリア |
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| Outline of Final Research Achievements |
This study was conducted to elucidate the relationship between the pathogenesis of Duchenne muscular dystrophy (DMD) and impaired mitochondria. mitochondrial DNA from skeletal muscle of DMD model mice was analyzed by next-generation sequencing, but deletion sites could not be identified. On the other hand, the nuclear localization of TFEB, an autophagy-related factor, was significantly reduced in the skeletal muscle of DMD model mice. In the future, we will clarify whether SIRT1 activation shifts the localization of TFEB to the nucleus in DMD. We will then elucidate the mitophagy-promoting mechanism via SIRT1 activation to develop a mitophagy-targeted therapy for muscular dystrophy.
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| Free Research Field |
薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果の意義は筋ジストロフィー(DMD)の病態をマイトファジーと障害ミトコンドリアの観点から解明し、根本的な治療法がないDMDの病態解明と新規治療法の開発に結びつく点である。本研究によりDMDにおけるマイトファジーの障害にTFEBの活性低下が関与している可能性を示すことができた。さらにSIRT1を介したTFEBの活性化がマイトファジーを標的としたDMDの治療に結びつく可能性を示すことができた。
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