Generation of the novel mouse model for Parkinson's disease derived from two-hit hypothesis

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461291
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: Funayama Manabu 順天堂大学, 医学部, 准教授 (70468578)
• Co-Investigator(Renkei-kenkyūsha): AMO Taku 防衛大学校, 応用化学科, 助教 (40453922)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: ミトコンドリア / パーキンソン病 / 電子伝達系 / 呼吸鎖複合体 / 感受性遺伝子

Outline of Final Research Achievements

To identify the molecules related vulnerability of dopaminergic neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity of NDUFV2 heterozygous knockout mice, I performed high throughput molecular profiling using isobaric tags for relative and absolute quantitation (iTRAQ) and liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses. A total of 17 proteins were identified as statistically different between wild-type and NDUFV2 heterozygous knockout mice in the midbrain of 48 hours after the MPTP administration. This results raise the possibility of discovering novel proteins related the pathogenesis of Parkinson’s disease (PD).
To analyze molecular phenotypes of CHCHD2, which have been reported as a novel causative gene for autosomal dominant PD, I generated CHCHD2 knockout SH-SY5Y cells using CRISPR-Cas9 system. CHCHD2 knockout SH-SY5Y cell was markedly decreased protein levels and activity of cytochrome c oxidase (Complex IV).

Free Research Field

分子遺伝学