2019 Fiscal Year Final Research Report
Establishment of ALS treatment strategy using Multi-omics technology
| Project/Area Number |
16H06247
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | Tokyo Medical 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 | ALS / C9orf72 |
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| Outline of Final Research Achievements |
In this study, we investigated the pathophysiology of polyPR peptide, produced from ALS-causative C9orf72 gene, and the treatment methods through comprehensive analysis of proteome and cytotoxic pathways. As a result, we found that polyPR accumulated in nucleoli and inhibited protein translation, and caused phase separation to inhibit the function of many proteins. In addition, we have identified a compound that suppresses the production of polyPR and we are continuing the experiments for future clinical application.
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| Free Research Field |
神経内科学
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| Academic Significance and Societal Importance of the Research Achievements |
我々はALSの最も重要な原因遺伝子であるC9orf72遺伝子産物polyPRの毒性機構解析を行い、特異的に核小体に集積し、蛋白翻訳抑制を介して神経細胞死を起こすことを見出した。本知見は様々なグループから追試されており、蛋白翻訳抑制はpoly-PRによる毒性機構として広く認知されている。また、今回同定したpolyPRの産生を抑制する化合物はすでに他疾患で臨床応用に向けた治験が進んでおり、臨床化されればその社会的意義は極めて大きい。
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