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Drug screening to improve mitochondrial functions

Research Project

Project/Area Number 16K15484
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionJuntendo 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  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
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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 / Parkin / PINK1 / iPS / ショウジョウバエ / スクリーニング / シグナル伝達 / 脳神経疾患 / 酵素
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.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (10 results)

All 2017 Other

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Invited: 2 results) Book (2 results) Remarks (1 results)

  • [Int'l Joint Research] Northwestern University(米国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Evidence that phosphorylated ubiquitin signaling is involved in the etiology of Parkinson’s disease2017

    • Author(s)
      Shiba-Fukushima Kahori、Ishikawa Kei-Ichi、Inoshita Tsuyoshi、Izawa Nana、Takanashi Masashi、Sato Shigeto、Onodera Osamu、Akamatsu Wado、Okano Hideyuki、Imai Yuzuru、Hattori Nobutaka
    • Journal Title

      Human Molecular Genetics

      Volume: 26 Pages: 3172-3185

    • DOI

      10.1093/hmg/ddx201

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ミトコンドリア機能障害とパーキンソン病2017

    • Author(s)
      今居 譲
    • Journal Title

      日本臨牀

      Volume: 75 Pages: 28-35

    • Related Report
      2016 Research-status Report
  • [Journal Article] 遺伝子から探るパーキンソン病病態へのミトコンドリアの関与2017

    • Author(s)
      今居 譲、柴佳保里、服部信孝
    • Journal Title

      医学のあゆみ

      Volume: 260 Pages: 85-91

    • Related Report
      2016 Research-status Report
  • [Presentation] ミトコンドリアの機能維持に関与するパーキンソン病遺伝子の解析2017

    • Author(s)
      今居 譲
    • Organizer
      ミトコンドリア機能研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] PINK1-Parkinシグナル伝達に関与する新規分子の解析2017

    • Author(s)
      柴 佳保里、井下 強、青木 裕子、石濱 泰、今居 譲、服部信孝
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] ミトコンドリアの機能維持に関与するパーキンソン病原因遺伝子の解析2017

    • Author(s)
      今居 譲
    • Organizer
      ミトコンドリア機能研究会
    • Place of Presentation
      大阪市
    • Related Report
      2016 Research-status Report
    • Invited
  • [Book] ミトコンドリア機能障害とパーキンソン病2017

    • Author(s)
      今居 譲
    • Total Pages
      168
    • Publisher
      日本臨牀
    • Related Report
      2017 Annual Research Report
  • [Book] 遺伝子から探るパーキンソン病病態へのミトコンドリアの関与2017

    • Author(s)
      今居 譲、柴佳保里、服部信孝
    • Total Pages
      127
    • Publisher
      医歯薬出版
    • Related Report
      2017 Annual Research Report
  • [Remarks] 順天堂大学 脳神経内科紹介

    • URL

      http://www.juntendo-neurology.com/n-kenkyu-syoukai.html

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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