Drug screening to improve mitochondrial functions

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15484
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: Imai Yuzuru 順天堂大学, 医学(系)研究科(研究院), 先任准教授 (30321730)
• Co-Investigator(Renkei-kenkyūsha): SHIBA Kahori (福嶋 佳保里) 順天堂大学, 医学研究科, 准教授 (30468582) ; INOSHITA Tsuyoshi 順天堂大学, 医学研究科, 助教 (20601206) ; OHBA Yusuke 北海道大学, 医学部, 教授 (30333503)
• Research Collaborator: ARANO Taku 順天堂大学, 医学研究科, 研究員 (80750091)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: ミトコンドリア / ドーパミン神経 / パーキンソン病 / 神経変性疾患 / 創薬

Outline of Final Research Achievements

The genes responsible for autosomal recessive early-onset Parkinson’s disease, Parkin and PINK1 encode a ubiquitin ligase and a mitochondrial protein kinase, respectively. A series of studies have revealed that Parkin in collaboration with PINK1 has a role for mitochondrial quality control, impairment of which leads to dopaminergic neurodegeneration. In this study, we aimed at searching drugs to improve mitochondrial functions through moderate activation of PINK1-Parkin signaling.
We developed a cell-based reporter assay to monitor PINK1-Parkin signaling and screened approximately 310-thousands of chemicals. Hit compounds obtained in the screening were further tested for mitochondrial membrane potential and cell viability and three candidates were identified as seed compounds.

Free Research Field

神経科学