Analysis of a molecular mechanism to improve polyglutamine diseases by activating alternative autophagy
| Project/Area Number |
15K08420
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
ARAKAWA Satoko 東京医科歯科大学, 難治疾患研究所, 講師 (90415159)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | オートファジー / ポリグルタミン病 / ケミカルバイオロジー / ゴルジ / オルタナティブオートファジー |
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| Outline of Final Research Achievements |
Autophagy is a cellular process that degrades subcellular constituents, and is conserved from yeast to mammals. Although autophagy is believed to be essential for living cells, cells lacking Atg5 or Atg7 are healthy, suggesting that a non‐canonical degradation pathway exists to compensate for the lack of autophagy. We first showed that the budding yeast lacking Atg5 undergoes bulk protein degradation using Golgi‐mediated structures to compensate for autophagy when treated with amphotericin B1 a polyene antifungal drug. We next identified Aag4 as a molecule essential for alternative autophagy, we clarified the mechanism of alternative autophagy and its physiological roles. Finally, we discovered several chemicals to induce alternative autophagy but not conventional autophagy. One of them reduced the polyglutamine aggregation in the cytosol, which causes polyglutamine diseases. We are currently observing the process of the aggregation formation and the drug effects on it using EM.
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Autophagy controls centrosome number by degrading Cep63.2016
Author(s)
Watanabe Y, Honda S, Konishi A, Satoko Arakawa S, Murohashi M, Yamaguchi H, Torii S, Tanabe M, Tanaka S, Warabi E, Shimizu S.
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Journal Title
Nature Communications
Volume: 7
Issue: 1
Pages: 13508-13508
DOI
NAID
Related Report
Peer Reviewed / Open Access
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