2010 Fiscal Year Final Research Report

Metabolic analysis in Drosophila models of neurodegenerative diseases

Research Project

Project/Area Number	21800064
Research Category	Grant-in-Aid for Research Activity Start-up
Allocation Type	Single-year Grants
Research Field	Nerve anatomy/Neuropathology
Research Institution	Waseda University
Principal Investigator	MATSUDA Nanami Waseda University, 先端科学・健康医療融合研究機構, 講師 (70360641)
Project Period (FY)	2009 – 2010
Keywords	神経変性疾患 / パーキンソン病 / 筋萎縮性軸索硬化症(ALS) / ショウジョウバエ / エネルギー代謝
Research Abstract	There is increasing evidence that neurodegenerative diseases are a symptom of a deficiency in the regulation of mitochondrial function and metabolism, however the mechanism has been unclear. Mitochondria, as the central organelles in metabolic regulation might have a role to play in the common etiology of neurodegeneration. To address the roles of metabolic defect in neurodegenerative diseases, we established RNA interference-mediated Drosophila parkin (dparkin) knockdown flies and Drosophila ALS2/alsin (dALS2) knockdown flies, for Parkinson's disease and juvenile onset recessive familial amyotrophic lateral sclerosis (ALS2) models, respectively. We demonstrate that nervous system-specific knockdown of dparkin or dALS2 caused shorter lifespan and lower locomotor activity. Currently we are exploring the relevance of abnormality of metabolism and mitochondrial dysfunction in neurodegenerative pathogenesis caused by deficiency of parkin or ALS2.