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Establishment of biomarker targeting neuromuscular junction in sarcopenia

Research Project

Project/Area Number 16K01851
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied health science
Research InstitutionTokyo Metropolitan Geriatric Hospital and Institute of Gerontology

Principal Investigator

Mori Shuuichi  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (30508677)

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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords神経筋シナプス / バイオマーカー / MuSK / 加齢・老化
Outline of Final Research Achievements

Several lines of evidence indicate disassembly of neuromuscular junction (NMJ) in aged muscles, suggesting that dying-back axonal degeneration is involved with pathology of sarcopenia as well as that of ALS. Therefore, development of biomarkers that reflects condition of NMJ is important for early detection and monitoring of altering motor function so that more timely interventions may ensure.
MuSK (muscle-specific kinase), a receptor-type tyrosine kinase, plays an essential role in maintaining integrity of NMJ. Although MuSK is a transmembrane protein, we detected extracellular region of MuSK protein in mouse serum. In this study, we demonstrated that serum MuSK protein has potential to more easily and accurately detect condition of NMJ using animal model for muscle atrophy and provide evidence that it is an available marker for evaluating progression and therapeutic benefit in preclinical studies of sarcopenia and ALS.

Academic Significance and Societal Importance of the Research Achievements

現在、筋量の低下を検出するために用いられている画像診断やバイオマーカーは長期間の経過観察を必要とする。一方、本研究で用いたバイオマーカーはサルコペニアの発症機序に基づく特異性の高い分子を標的とするため、その変化は「筋量」ではなく「筋萎縮に至るシグナル」を反映することになる。それ故、筋萎縮の前駆症状を既存のバイオマーカーよりも短期間の観察で簡易的に検出することが可能である。これにより、筋萎縮の早期の検出と治療開始が可能になっていくと考えられる。

Report

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

    (18 results)

All 2019 2018 2017 2016

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (10 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Utility of experimental animal models of myasthenia gravis for the elucidation of pathogenic mechanisms and development of new medications.2019

    • Author(s)
      Mori S, Shigemoto K.
    • Journal Title

      Clinical and Experimental Neuroimmunology

      Volume: 印刷中 Issue: 2 Pages: 85-95

    • DOI

      10.1111/cen3.12517

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tbx1 regulates inherited metabolic and myogenic abilities of progenitor cells derived from slow- and fast-type muscle2018

    • Author(s)
      Motohashi Norio、Uezumi Akiyoshi、Asakura Atsushi、Ikemoto-Uezumi Madoka、Mori Shuuichi、Mizunoe Yuhei、Takashima Rumi、Miyagoe-Suzuki Yuko、Takeda Shin’ichi、Shigemoto Kazuhiro
    • Journal Title

      Cell Death & Differentiation

      Volume: 印刷中 Issue: 6 Pages: 1024-1036

    • DOI

      10.1038/s41418-018-0186-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] サルコペニア・フレイルのメカニズムと脳卒中.2018

    • Author(s)
      重本 和宏, 森 秀一, 本橋 紀夫, 高嶋 留美.
    • Journal Title

      分子脳血管病

      Volume: 17 Pages: 119-122

    • Related Report
      2018 Annual Research Report
  • [Journal Article] フレイルのバイオマーカー探索.2018

    • Author(s)
      重本 和宏, 森 秀一, 本橋 紀夫, 高嶋 留美.
    • Journal Title

      診断と治療のABC

      Volume: 137 Pages: 67-73

    • Related Report
      2018 Annual Research Report
  • [Journal Article] サルコペニアの概念とその診断方法.2018

    • Author(s)
      重本 和宏, 森 秀一, 本橋 紀夫, 高嶋 留美.
    • Journal Title

      病理と臨床

      Volume: 36 Pages: 128-134

    • Related Report
      2018 Annual Research Report
  • [Journal Article] サルコペニア・フレイルの基礎研究の現状.2018

    • Author(s)
      重本 和宏, 森 秀一, 本橋 紀夫, 高嶋 留美.
    • Journal Title

      日本臨床

      Volume: 76

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Immunization of mice with LRP4 induces myasthenia similar to MuSK-associated myasthenia gravis.2017

    • Author(s)
      Mori S, Motohashi N, Takashima R, Kishi M, Nishimune H, Shigemoto K.
    • Journal Title

      Experimental Neurology

      Volume: 297 Pages: 158-167

    • DOI

      10.1016/j.expneurol.2017.08.006

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dual-color STED microscopy reveals a sandwitch structure of Bassoon and Piccolo in active zones of adult and aged mice.2016

    • Author(s)
      Nishimune H, Badwi Y, Mori S, Shigemoto K
    • Journal Title

      Scientific Report

      Volume: 6,27935 Issue: 1

    • DOI

      10.1038/srep27935

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Inter-muscular injection of m. triangularis sterni: A new ex vivo evaluation of mouse NMJ.2018

    • Author(s)
      Kishi M, Mori S, Shigemoto K, Sakakibara R, Tateno F, Aiba Y, Konishi T.
    • Organizer
      第59回日本神経学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 筋線維タイプを識別できるMusColorマウスの開発.2018

    • Author(s)
      本橋 紀夫, 森 秀一, 高嶋 留美, 重本 和宏.
    • Organizer
      第4回日本筋学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A new ex vivo electrophysiological neuromuscular evaluation - In case of Guillain-Barre syndrome.2018

    • Author(s)
      Kishi M, Mori S, Koga M, Shigemoto K, Konishi T, Sakakibara R, Tateno F, Aiba Y.
    • Organizer
      14th International Congress of Neuroimmunology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] NMJ由来タンパク質の血中バイオマーカーとしての有用性の検討.2018

    • Author(s)
      森 秀一, 本橋 紀夫, 高嶋 留美, 岸 雅彦, 重本 和宏.
    • Organizer
      第73回日本体力医学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Generation of experimental model of myasthenia gravis anti-LRP4 antibodies via active immunization.2017

    • Author(s)
      Mori S, Motohashi N, Takashima R, Kishi M, Nishimune H, Shigemoto K.
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Lrp4の機能抑制による神経筋刺激伝達の変化.2017

    • Author(s)
      森 秀一, 本橋 紀夫, 高嶋 留美, 岸 雅彦, 重本 和宏.
    • Organizer
      第72回日本体力医学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 抗Lrp4抗体陽性重症筋無力症の自己免疫動物モデルの作成と病態解析.2017

    • Author(s)
      森 秀一, 本橋 紀夫, 高嶋 留美, 重本 和宏.
    • Organizer
      第5回若手による骨格筋細胞研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] 新規筋繊維タイプ変換誘導因子の探索.2016

    • Author(s)
      本橋 紀夫, 森 秀一, 山崎 綾乃, 高嶋 留美, 重本 和宏.
    • Organizer
      第4回若手による骨格筋細胞研究会
    • Place of Presentation
      ウインクあいち (愛知県・名古屋市)
    • Year and Date
      2016-11-14
    • Related Report
      2016 Research-status Report
  • [Presentation] microRNAによる骨格筋管細胞の維持機構.2016

    • Author(s)
      本橋 紀夫, 森 秀一, 高嶋 留美, 重本 和宏.
    • Organizer
      第71回日本体力医学会大会
    • Place of Presentation
      いわて県民情報交流センター (岩手県・盛岡市)
    • Year and Date
      2016-09-23
    • Related Report
      2016 Research-status Report
  • [Presentation] 筋線維タイプと骨格筋管細胞維持機構の関連.2016

    • Author(s)
      本橋 紀夫, 森 秀一, 高嶋 留美, 重本 和宏.
    • Organizer
      第2回日本筋学会学術集会
    • Place of Presentation
      国立精神・神経医療研究センター (東京都・小平市)
    • Year and Date
      2016-08-05
    • Related Report
      2016 Research-status Report

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

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