2016 Fiscal Year Final Research Report
Implication of Synoviolin on Limb-Girdles Muscle Dystrophy.
| Project/Area Number |
15K15091
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | 分子病理学 / 筋ジストロフィー / 創薬開発 / タンパク質分解系 / ユビキチン |
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| Outline of Final Research Achievements |
The functional discrepancy in missense mutation between in vitro and in vivo remains to be uncovered. To explain this observation, protein degradation system has been interested. For example, type2 Limb-Girdle Muscle dystrophy is known to be caused by missense mutant of α-sarcoglycan gene. The missense mutant type protein has approximately 30% of residual activity in vitro but the protein is not detected in cell, and Synoviolin plays a crucial role in the degradation of missense α-sarcoglycan protein.
To develop the innovative therapy, we attempted to understand the physiological and pathological role of Synoviolin. By using muscle-specific its knock out mice, we found the gene plays an important role in muscle. We previously developed Synoviolin inhibitor and this inhibitor had protective effect on muscle atrophy model. These two data clearly indicate Synoviolin as a therapeutic target of muscle diseases including Limb-Girdle muscle dystrophy and muscle atrophy.
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| Free Research Field |
内科学、分子生物学
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