2010 Fiscal Year Final Research Report

Analysis of the mechanism of Parkinson disease and drug development using the nematode C.elegans

Research Project

Project/Area Number	21700393
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Nerve anatomy/Neuropathology
Research Institution	The University of Tokyo
Principal Investigator	KUWAHARA Tomoki The University of Tokyo, 大学院・薬学系研究科, 特任研究員 (10533903)
Project Period (FY)	2009 – 2010
Keywords	パーキンソン病 / α-synuclein / リン酸化 / 線虫
Research Abstract	α-Synuclein is a causative gene for familial Parkinson's disease and its protein product accumulates in the neurons of affected brains with phosphorylation at Ser129. Nematode C. elegans is suggested as a useful tool for the analysis of the molecular mechanisms of neurodegenerative diseases. We have studied the role of phosphorylation of α-synuclein in its neurotoxicity using nematodes expressing human α-synuclein. Our results suggest that the phosphorylation at Ser129 functions against α-synuclein neurotoxicity and downstream stress response by lowering its membrane-binding property. We also found that the present nematode model is useful in further screening for modifier genes or therapeutic drugs.