Search of essential substrates of Parkin in Parkinsonism

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19523
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: Arano Taku 順天堂大学, 医学(系)研究科(研究院), 博士研究員 (80750091)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: Parkin / ドーパミン神経 / ミトコンドリア / CHCHD2 / ユビキチン / パーキンソン病 / ショウジョウバエ

Outline of Final Research Achievements

The parkin genes responsible for autosomal recessive early-onset Parkinson’s disease, which encodes ubiquitin-ligase, is known to regulate mitochondrial quality control. However, the pathogenesis of selective dopaminergic neuron death caused by Parkin mutations remained unknown. To address this issue, I tried to search dopaminergic neuron-specific or glia-specific ubiquitination substrates of Parkin using the combination of BioUb6-BirA system and Drosophila.
Newly identified autosomal dominant late-onset Parkinson’s disease gene, CHCHD2, encodes a mitochondrial protein with unknown functions. I tried to determine CHCHD2-binding proteins from human cultured cells and isolated a mitochondrial matrix protein p32. The biological significance of CHCHD2-p32 interaction was assessed using Drosophila models.

Free Research Field

分子生物学