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Loss of mitochondria quality control induce dopaminergic neurodegeneration

Research Project

Project/Area Number 19K07850
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionJuntendo University

Principal Investigator

Sato Shigeto  順天堂大学, 医学部, 先任准教授 (00445537)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsパーキンソン病 / ミトコンドリア / ドーパミン細胞 / 神経変性 / Parkin / CHCHD2 / モデルマウス / 神経細胞死 / WDR45 / モデル動物 / ドーパミン / マウス
Outline of Research at the Start

本研究では、パーキンソン病発症機序におけるミトコンドリア障害説の解を求めるため、ミトコンドリア可視化の技術を応用した動物モデル作成、および神経細胞での変異ミトコンドリアの動態解析を行うことを目的とする。これによる、パーキンソン病モデルマウスの確立は変異ミトコンドリアを生み出す根本原因(内的要因)の探索をも可能とし、老化や孤発性パーキンソン病の実態に迫ることが期待される。

Outline of Final Research Achievements

Parkin knockout mice and CHCHD2 knockout mice showed motor symptoms and dopaminergic neuronal loss over the age of 100 weeks. Fragmented and damaged mitochondria accumulated in the substantia nigra dopaminergic cells in the aged mice, suggesting that increased vulnerability of dopaminergic cells is involved in neuronal cell death.

Academic Significance and Societal Importance of the Research Achievements

モデルマウスの解析から不良なミトコンドリアの蓄積がパーキンソン病の原因であることが有力となり、古くから指摘されてきたミトコンドリア障害説を裏付ける結果となった。このモデルマウスの利用はミトコンドリアをターゲットとした治療法の開発に有益である。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (7 results)

All 2021 2020 2019

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 6 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Homeostatic p62 levels and inclusion body formation in CHCHD2 knockout mice2021

    • Author(s)
      Sato S, Noda S, Torii S, Amo T, Ikeda A, Funayama M, Yamaguchi J, Fukuda T, Kondo H, Tada N, Arakawa S, Watanabe M, Uchiyama Y, Shimizu S, Hattori N
    • Journal Title

      Hum Mol Genet.

      Volume: 30 Pages: 443-453

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PARKIN modifies peripheral immune response and increases neuroinflammation in active experimental autoimmune encephalomyelitis (EAE)2021

    • Author(s)
      Cossu D, Yokoyama K, Sato S, Noda S, Sechi LA, Hattori N.
    • Journal Title

      J Neuroimmunol.

      Volume: 359 Pages: 577694-577694

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of Parkin contributes to mitochondrial turnover and dopaminergic neuronal loss in aged mice2020

    • Author(s)
      Noda S, Sato S, Fukuda T, Tada N, Uchiyama Y, Tanaka K, Hattori N
    • Journal Title

      Neurobiol Dis.

      Volume: 136 Pages: 104717-104717

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Variants in saposin D domain of prosaposin gene linked to Parkinson's disease.2020

    • Author(s)
      Oji Y, Hatano T, Ueno SI, Funayama M, Ishikawa KI, Okuzumi A, Noda S, Sato S, Satake W, Toda T, Li Y, Hino-Takai T, Kakuta S, Tsunemi T, Yoshino H, Nishioka K, Matsuda J, Hattori N
    • Journal Title

      Brain

      Volume: 143 Pages: 1190-1205

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aging-related motor function and dopaminergic neuronal loss in C57BL/6 mice.2020

    • Author(s)
      Noda S, Sato S, Fukuda T, Tada N, Hattori N
    • Journal Title

      Mol Brain.

      Volume: 13 Pages: 46-46

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of Parkin contributes to mitochondrial turnover and dopaminergic neuronal loss in aged mice.2020

    • Author(s)
      Noda S, Sato S, Fukuda T, Tada N, Uchiyama Y, Tanaka K, Hattori N.
    • Journal Title

      Neurobiol Dis.

      Volume: 136 Pages: 104717-104717

    • DOI

      10.1016/j.nbd.2019.104717

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Patent(Industrial Property Rights)] パーキンソン病モデル非ヒト動物2019

    • Inventor(s)
      佐藤栄人、野田幸子、服部信孝
    • Industrial Property Rights Holder
      佐藤栄人、野田幸子、服部信孝
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-154898
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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