2019 Fiscal Year Final Research Report
Investigation of molecular pathogenesis and development of therapeutic methods for Fukuyama muscular dystrophy and related diseases
| Project/Area Number |
16H05353
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Keywords | 糖鎖 / 筋ジストロフィー / 脳神経疾患 / 酵素 / 遺伝子 / ジストログリカノパチー / fukutin / α-dystroglycan |
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| Outline of Final Research Achievements |
In this study, we aimed to delineate the full O-Man glycan structure of a-dystroglycan (a-DG) whose abnormalities cause muscular dystrophy, to clarify the biosynthesis pathway of the glycan, to understand the pathogenesis of neuronal dysfunction of the disease, and to explore its therapeutic possibility. We determined the unknown glycan structure that contained ribitol phosphate. We also identified the functions of four gene proteins such as fukutin that are responsible for muscular dystrophy, and determined the biosynthesis pathway for ribitol phosphate of the glycan. We could not find novel proteins modified with the O-Man glycan or a-DG ligands. Some therapeutic strategies were found to be effective for the disease model cells and mice. Further investigations are required.
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| Free Research Field |
人類遺伝学、遺伝医学、ゲノム医科学
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| Academic Significance and Societal Importance of the Research Achievements |
α-DGのO-Man型糖鎖の完全構造と生合成機構を明らかにしたことで、重篤なα-DGpathyの発症機序を理解でき、新たな治療標的発見、有効な治療法開発につながる。新たな翻訳後修飾の発見であり、医学的のみならず生物学的にも学術的な意義がある。また、O-Man型糖鎖と脳奇形・神経機能との関連を示し、神経機能障害の治療の有効性が示されれば、問題の多い胎児治療ではなく、生後の治療が可能になり、実現可能な脳の治療法の構築につながることが期待でき、社会的意義が大きい。
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