| Project/Area Number |
17H01532
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
植田 亮 東京大学, 医科学研究所, 助教 (10445025)
手塚 徹 東京大学, 医科学研究所, 助教 (50312319)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥41,860,000 (Direct Cost: ¥32,200,000、Indirect Cost: ¥9,660,000)
Fiscal Year 2019: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2018: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2017: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
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| Keywords | 神経筋シナプス / シグナル伝達 / 神経科学 / 細胞内シグナル伝達 / 運動機能障害 |
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| Outline of Final Research Achievements |
We previously demonstrated that the activation of the muscle-specific receptor kinase MuSK by the cytoplasmic protein Dok-7 is essential for NMJ formation, and that mutations in the human DOK7 gene underlie NMJ synaptopathy (DOK7 myasthenia). Moreover, we developed a novel therapeutic approach that enhances NMJ formation in living animals. In this study, we aimed to understand molecular mechanisms underlying NMJ formation and pathophysiological significance of NMJ defects associated with muscle weakness and motor dysfunction. Indeed, we successfully identified signaling molecules that regulate NMJ formation. Also, we demonstrated that the above-mentioned novel therapeutic approach enhances innervation at NMJs together with muscle strength and motor activity in aged mice, demonstrating pathophysiological significance of age-related NMJ defects.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果は、独自に開発したNMJ形成増強治療が、多様な要因により惹起される加齢性の筋力・運動機能の低下に有効である可能性を提示するものであり、高齢化社会における生活の質の向上に資する医療技術としての発展が期待される点において高度な社会的意義を有している。さらに、本研究は我々の運動機能制御に必須のNMJについて、その成り立ちや病態、治療メカニズムの理解を深める点においても大きな学術的意義を有する。
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