2016 Fiscal Year Final Research Report
Elucidation of the molecular mechanism of ALS pathogenesis mediated by cytoplasmic RNA.
| Project/Area Number |
15K18365
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Tohoku 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 | 筋萎縮性側索硬化症（ALS） / TDP-43 / 細胞内凝集体形成 / RNA / RNA分解酵素 |
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| Outline of Final Research Achievements |
Nearly all of the amyotrophic lateral sclerosis (ALS) patients contain cytoplasmic aggregation of TDP-43 in their neuronal tissues. Although aggregated TDP-43 was shown to contribute to the ALS pathogenesis, the molecular mechanism by which TDP-43 forms cytoplasmic aggregation are not fully understood. We found that the mutation of TDP-43 which disrupted the association with RNA significantly reduced cytoplasmic aggregation. Furthermore, TDP-43 fused with RNase exhibited the resistance to aggregation formation. These results revealed that RNA is critical for TDP-43 to form cytoplasmic aggregation and offered the novel therapeutic strategy for the treatment of ALS.
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| Free Research Field |
ユビキチン化を介したタンパク質および核酸制御
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