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 |
Research Field |
Nerve anatomy/Neuropathology
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Research Institution | Tohoku University |
Principal Investigator |
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Project Period (FY) |
2015-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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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 / ALS / RNase |
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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Report
(3 results)
Research Products
(11 results)
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[Journal Article] The SCFβ-TRCP E3 ubiquitin ligase complex targets Lipin1 for ubiquitination and degradation to promote hepatic lipogenesis.2017
Author(s)
Shimizu K, Fukushima H, Ogura K, Lien EC, Nihira NT, Zhang J, North BJ, Guo A, Nagashima K, Nakagawa T, Hoshikawa S, Watahiki A, Okabe K, Yamada A, Toker A, Asara JM, Fukumoto S, Nakayama KI, Nakayama K, Inuzuka H, Wei W.
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Journal Title
Sci Signal. doi: 10.1126/scisignal.aah4117.
Volume: 10
Issue: 460
Pages: 1-15
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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