Analysis of a molecular mechanism to improve polyglutamine diseases by activating alternative autophagy

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08420
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: ARAKAWA Satoko 東京医科歯科大学, 難治疾患研究所, 講師 (90415159)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: オートファジー / ポリグルタミン病

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.

Free Research Field

微細構造