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Significance of dystroglycan processing and its participation in the pathogenesis of neuromuscular disorders

Research Project

Project/Area Number 16K09682
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionTeikyo University

Principal Investigator

Matsumura Kiichiro  帝京大学, 医学部, 教授 (50260922)

Co-Investigator(Kenkyū-buntansha) 真先 敏弘  帝京科学大学, 医学教育センター, 教授 (00585028)
萩原 宏毅  帝京科学大学, 医療科学部, 教授 (80276732)
Research Collaborator Saito Fumiaki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords筋ジストロフィー / ジストログリカン / インフルエンザ / A型インフルエンザ / 糖鎖修飾 / 蛋白質プロセッシング / 脳神経疾患
Outline of Final Research Achievements

α-Dystroglycanopathy, a type of muscular dystrophy, is caused by abnormal post-translational modifications. Although the N-terminal domain of α-dystroglycan (α-DG-N) is secreted from cells by processing, the function of secreted α-DG-N remains unknown. This study was performed to elucidate the function. α-DG-N was presumed to affect the extension of neurites in central nervous system by the results of a previous report. However, this function was not ascertained in vivo using gene-modified mice. On the other hands, an unexpected function of α-DG-N was revealed. Indeed, α-DG-N inhibits infection of influenza virus. Thus, it is possible that α-DG-N may be applied to the therapy of influenza infection in the future.

Academic Significance and Societal Importance of the Research Achievements

α-ジストログリカンのN末端ドメイン(α-DG-N)の機能はこれまで不明であった。しかし今回の研究によってインフルエンザウイルスの増殖を抑制するという思いがけない作用を有することが明らかとなった。インフルエンザは全世界で毎年300-500万人が罹患し、その結果25-50万人が死亡していると推定されている。また先進国においてもインフルエンザによる高齢者の死亡が問題となっている。今後α-DG-Nを用いたインフルエンザに対する新たな治療法開発への道が開かれるかもしれない。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (6 results)

All 2019 2018 2017 2016

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Protective role for the N-terminal domain of α-dystroglycan in Influenza A virus proliferation2019

    • Author(s)
      Jessica C. de Greef, Bram Slutterd, Mary E. Andersona, Rebecca Hamlyn, Raul O’Campo Landaa, Ellison J. McNutta, Yuji Haraa, Lecia L. Pewe, David Venzke, Kiichiro Matsumura, Fumiaki Saito, John T. Hartyd, Kevin P. Campbell
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 166 Issue: 23 Pages: 11396

    • DOI

      10.1073/pnas.1904493116

    • URL

      https://pure.teikyo.jp/en/publications/9605d02f-81cd-4344-8c75-5686ef2d67a1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Role of dystroglycan in limiting contraction-induced injury to the sarcomeric cytoskeleton of mature skeletal muscle.2016

    • Author(s)
      Rader EP, Turk R, Willer T, Beltran D, Inamori K, Peterson TA, Engle J, Prouty S, Matsumura K, Saito F, Anderson ME, Campbell KP
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 113 Issue: 39 Pages: 10992-10997

    • DOI

      10.1073/pnas.1605265113

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Excision of myotonic dystrophy CTG repeat by CRISPR/Cas9 double nicking.2018

    • Author(s)
      斉藤史明、萩原宏毅、真先敏弘、池田美樹、清水輝夫、松村喜一郎、園生雅弘
    • Organizer
      第59回日本神経学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Excision of expanded CTG repeat of myotonic dystrophy with CRISPR/Cas9 genome editing.2017

    • Author(s)
      Saito F, Ikeda M, Hagiwara H, Masaki T, Matsumura K. Sonoo M.
    • Organizer
      23rd World congress of neurology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Tubular aggregate myopathy caused by a novel mutation in the cytoplasmic domain of STIM1.2016

    • Author(s)
      Saito F, Okuma H, Mitsui J, Hara Y, Hatanaka Y, Ikada M, Shimizu T, Matsumura K, Shimizu J, Tsuji S, Sonoo M
    • Organizer
      21st International congress of the World Muscle Society
    • Place of Presentation
      スペイン・グラナダ
    • Year and Date
      2016-10-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Novel mutation of STIM1 causes dysregulation of Ca2+ homeostasis in tubular aggregate myopathy.2016

    • Author(s)
      斉藤史明、原雄二、三井純、畑中裕己、萩原宏毅、真先敏弘、清水輝夫、清水潤、辻省次、松村喜一郎、園生雅弘
    • Organizer
      第57回日本神経学会学術大会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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