Polyglutamine oligomers in human brain play a crucial role in the pathogenesis of polyglutamine diseases.

Research Project

Project/Area Number	23591235
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Neurology
Research Institution	Niigata University
Principal Investigator	TAKAHASHI Toshiaki 新潟大学, 脳研究所, 非常勤講師 (70377191)
Co-Investigator(Renkei-kenkyūsha)	TADA Masayoshi 新潟大学, 脳研究所, 助教 (10467079) KATADA Shinnichi 新潟大学, 医歯学総合病院, 特任助教 (70599167)
Project Period (FY)	2011 – 2013
Project Status	Completed (Fiscal Year 2013)
Budget Amount *help	¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000) Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords	polyglutamine / oligomer / DRPLA / C.elegans / SDD-AGE / ポリグルタミン病 / 重合体 / 神経変性
Research Abstract	Expanded polyglutamine proteins cause neurodegenerative disorders. Although polyglutamine oligomers have been proposed as a cytotoxic structure, the cytotoxicity of polyglutamine oligomers, not inclusion bodies, has not been proven in human brain tissue. To clarify the cytotoxicity of polyglutamine oligomers, we carried out Semi-Denaturing Detergent-Agarose Gel Electrophoresis (SDD-AGE) and detected oligomers in autopsy brain tissue in DRPLA patients. Quantitative analysis indicates that accumulation of polyglutamine oligomers correlate with the severity of neuronal loss in human brain tissue. These results show that oligomers in human brain play a crucial role in the pathogenesis of polyglutamine diseases.