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Elucidation of the mechanism of dopaminergic cell death based on the analysis of a novel mouse model of Parkinson's disease.

Research Project

Project/Area Number 19K16914
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Ikuno Masashi  京都大学, 医学研究科, 特定助教 (30808960)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsパーキンソン病 / アルファシヌクレイン / 神経細胞死 / モデルマウス / 前駆病態
Outline of Research at the Start

本研究の目的はパーキンソン病における神経細胞死のメカニズムを明らかにすることである。パーキンソン病でみられる異常たんぱく質の蓄積とドパミン神経細胞死を来す新規の2種類のモデルマウスを用い、脂質解析や広範囲での代謝産物測定、遺伝子発現解析を行う。これにより生体内でドパミン神経特異的な神経細胞死が起こる機序を明らかにする。本研究の成果はパーキンソン病の発症や進行を抑制する治療に繋がることが期待できる。

Outline of Final Research Achievements

In order to prevent the onset or progression of Parkinson's disease, it is important to understand the pathogenesis of the disease in the prodromal phase, before the dopamine nerves are reduced in large amounts. It is known that Parkinson's disease manifests various abnormalities in areas other than the brain from the prodromal stage. In this study, I used a mouse model of Parkinson's disease in the prodromal stage and analyzed its blood metabolites. The results showed an increase in isobutyricarnitine and pyrimidine nucleosides, which are thought to be associated with mitochondrial abnormalities. These results suggest that systemic mitochondrial dysfunction already exists in Parkinson's disease, even in its prodromal stage.

Academic Significance and Societal Importance of the Research Achievements

近年、パーキンソン病を始めとした中枢神経疾患における中枢神経以外の臓器との関連が注目されています。特にパーキンソン病では腸脳連関と言って脳の病態と腸管の状況が関連していることが知られています。本研究はパーキンソン病モデルマウスでも脳以外の異常が存在することを示すとともに、パーキンソン病の予防のための前駆期・全身病態の重要性を示唆する成果であると言えます。

Report

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

    (4 results)

All 2021 2020

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (3 results)

  • [Journal Article] Mitochondrial dysfunction in a mouse model of prodromal Parkinson’s disease: A metabolomic analysis2021

    • Author(s)
      Ikuno Masashi、Yamakado Hodaka、Amano Ikuko、Hatanaka Yusuke、Uemura Norihito、Matsuzawa Shu-ichi、Takahashi Ryosuke
    • Journal Title

      Neuroscience Letters

      Volume: 765 Pages: 136267-136267

    • DOI

      10.1016/j.neulet.2021.136267

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Presentation] パーキンソン病モデルマウスの血漿を用いたメタボローム解析2021

    • Author(s)
      生野真嗣
    • Organizer
      第14回パーキンソン病・運動障害疾患コングレス
    • Related Report
      2021 Annual Research Report
  • [Presentation] パーキンソン病モデルマウスの血漿を用いたメタボローム解析2021

    • Author(s)
      生野真嗣
    • Organizer
      第14回MDSJ
    • Related Report
      2020 Research-status Report
  • [Presentation] Mitochondrial dysfunction in mice model for prodromal Parkinson's disease: a metabolomic analysis2020

    • Author(s)
      Masashi Ikuno
    • Organizer
      第61回日本神経学会学術大会
    • Related Report
      2020 Research-status Report

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

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