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Towards understanding of novel molecular mechanisms regulating oligodendrocyte differentiation and myelination

Research Project

Project/Area Number 19K16268
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 46010:Neuroscience-general-related
Research InstitutionKindai University

Principal Investigator

Ishino Yugo  近畿大学, 東洋医学研究所, 助教 (80625088)

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 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsオリゴデンドロサイト / アルギニンメチル化 / PRMTs / PRMT4 / 髄鞘 / ミエリン / PRMT / タンパクメチル化 / タンパクリン酸化 / カルシニューリン
Outline of Research at the Start

脳内には神経細胞だけでなくグリア細胞も多数存在している。グリア細胞の一つであるオリゴデンドロサイト(OL)は、神経細胞の軸索にミエリンと呼ばれる絶縁体を形成することで、神経細胞間の高速で精緻な連絡を可能としている。これまでの精神疾患患者死後脳の解析等から、OL数の減少やミエリン形成異常・OL関連遺伝子の発現変動が見出されており、OLの機能低下による神経細胞間のコミュニケーション障害を起因とした精神疾患発症の可能性が注目されるようになってきた。本研究では、OL機能制御機構の一端を解明することで、精神疾患発症機構の解明および新規治療方法の確立への足がかりを見出す。

Outline of Final Research Achievements

Protein arginine methylation has been recognized as one of key posttranslational modifications, which is mediated by protein arginine methyltransferases (PRMTs). Although arginine-methylated proteins are highly expressed in the brain, the expression and function of PRMTs have remained largely unknown. In this study, we revealed that CARM1, one of PRMTs, regulates proliferation, differentiation and myelination of oligodendrocytes during the early brain development.

Academic Significance and Societal Importance of the Research Achievements

本研究によってアルギニンメチル化酵素の1つであるCARM1が発達期オリゴデンドロサイトの分化・成熟に重要なことが始めて明らかとなった。オリゴデンドロサイトの機能制御を担う新たな遺伝子を見出したものであり、今後、脳内のアルギニンメチル化タンパク質の重要性を理解する上で重要な知見となる。

Report

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

    (4 results)

All 2022 2021 2020 2019

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

  • [Journal Article] Coactivator-associated arginine methyltransferase 1 controls oligodendrocyte differentiation in the corpus callosum during early brain development.2022

    • Author(s)
      Ishino Y, Shimizu S, Tohyama M, Miyata S.
    • Journal Title

      Developmental Neurobiology

      Volume: Epub Issue: 3 Pages: 245-260

    • DOI

      10.1002/dneu.22871

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Presentation] Towards understanding of novel molecular mechanisms regulating oligodendrocyte differentiation and myelination2021

    • Author(s)
      Ishino Yugo、Shimizu Shoko、Tohyama Masaya、Miyata Shingo
    • Organizer
      第64回 日本神経化学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Towards understanding of novel molecular mechanisms regulating oligodendrocyte differentiation and myelination2020

    • Author(s)
      Yugo Ishino
    • Organizer
      The Japanese Society for Neurochemistry
    • Related Report
      2020 Research-status Report
  • [Presentation] Towards understanding of novel molecular mechanisms underlying oligodendrocyte properties both in normal and pathological condition2019

    • Author(s)
      石野雄吾
    • Organizer
      Neuro2019
    • Related Report
      2019 Research-status Report

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

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