Elucidation of the molecular mechanisms of muscle atrophy

2011 Fiscal Year Final Research Report

• Project/Area Number: 21200023
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry; Applied health science
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: SHIGEMOTO Kazuhiro 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, 研究部長 (40284400)
• Co-Investigator(Kenkyū-buntansha): KUBO Sachiho 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, 助手 (00280769) ; MIYAZAKI Tsuyoshi 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 (50376480) ; YAMADA Shigeru 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 (50508679)
• Project Period (FY): 2009 – 2011
• Keywords: 筋萎縮 / 神経筋シナプス / 逆行性シグナル / 運動神経細胞 / 筋線維

Research Abstract

We found that MuSK molecules, which are expressed at post synaptic membrane of NMJs, mediates unknown retrograde signaling which regulate presynaptic functions. We generated mouse expressed-genes database for atrophy-induced muscles to find the retrograde-signaling molecules.

Research Products

• [Journal Article] 3,4-Diaminopyridine improves neuromuscular transmission in a MuSK antibody-induced mouse model of myasthenia gravis (2012)
  • Author(s): Mori, S. , Kishi, M., Kubo, S., Akiyoshi, T., Yamada, S., Miyazaki, T., Konishi, T., Maruyama, N., and Shigemoto, K.
  • Journal Title: Journal of neuroimmunology Volume: 245 Pages: 75-78
  • DOI: DOI:10.1016/j.jneuroim.2012.02.010
  • Peer Reviewed
• [Journal Article] Antibodies against muscle-specific kinase impair both presynaptic and postsynaptic functions in a murine model of myasthenia gravis (2012)
  • Author(s): Mori, S., Kubo, S., Akiyoshi, T., Yamada, S., Miyazaki, T., Hotta, H., Desaki, J., Kishi, M., Konishi, T., Nishino, Y., Miyazawa, A., Maruyama, N., and Shigemoto, K.
  • Journal Title: The American journal of pathology Volume: 180 Pages: 798-810
  • DOI: DOI:10.1016/i.ajpath.2011.10.031
  • Peer Reviewed
• [Journal Article] Divalent and monovalent autoantibodies cause dysfunction of MuSK by distinct mechanisms in a rabbit model of myasthenia gravis (2012)
  • Author(s): Mori, S. , Yamada, S., Kubo, S. , Chen, J., Matsuda, S. , Shudou, M. , Maruyama, N., and Shigemoto, K.
  • Journal Title: Journal of neuroimmunology Volume: 244 Pages: 1-7
  • DOI: doi:10.1016/j.jneuroim.2011.12.005
  • Peer Reviewed
• [Journal Article] サルコペニアの発症機構 (2011)
  • Author(s): 重本和宏,森秀一,宮崎剛,久保幸穂
  • Journal Title: 神経内科 Volume: 75(6) Pages: 584-588
• [Journal Article] シナプスを介したサルコペニアの発症メカニズムとバイオマーカー (2011)
  • Author(s): 重本和宏、森秀一、宮崎剛、久保幸穂
  • Journal Title: 日本老年医学会雑誌 Volume: 48(1) Pages: 42-43
• [Journal Article] 運動神経細胞とサルコペニア (2011)
  • Author(s): 重本和宏、森秀一、宮崎剛、久保幸穂
  • Journal Title: Modern Physician Volume: 131,No.11 Pages: 1308-11
• [Journal Article] Muscle weakness and neuromuscular junctions in aging and disease (2010)
  • Author(s): Shigemoto, K., Kubo, S., Mori, S., Yamada, S., Akiyoshi, T., and Miyazaki, T.
  • Journal Title: Geriatr Gerontol Int 10 Suppl Volume: 1 Pages: 137-147
  • DOI: DOI:10.1111/j.1447-0594.2010.00608.x
  • Peer Reviewed
• [Journal Article] 抗MuSK抗体 (2010)
  • Author(s): 大田潔江,大田光煕,重本和宏、(他一名)
  • Journal Title: 日本臨床 Volume: Vol.685 Pages: Suppl.633-6
• [Journal Article] 神経筋接合部の異常と筋萎縮 (2010)
  • Author(s): 重本和宏,森秀一,久保幸穂,山田茂,秋好沢諭,宮崎剛
  • Journal Title: メジカルビュー社老年医学 Volume: update 2010-2011 Pages: 135-144
• [Journal Article] 神経筋接合部位の異常と筋力低下 (2009)
  • Author(s): 重本和宏、久保幸穂、丸山直記
  • Journal Title: 日本老年医学会雑誌 Volume: 46(2) Pages: 106-113
• [Journal Article] サルコペニア(加齢性筋肉減少症)とそのバイオマーカー (2009)
  • Author(s): 重本和宏、丸山直記
  • Journal Title: 老年医学 Volume: 47(6) Pages: 733-735
• [Presentation] A new synchronized model of myasthenia gravis caused by and-MuSK antibodies (2012)
  • Author(s): Shigemoto, K.
  • Organizer: International Conference on Nervous System Autoimmunity
  • Place of Presentation: Bangalore, India
  • Year and Date: 20120127-30
• [Presentation] 抗MuSK抗体陽性重症筋無力症の発症メカニズムに基づく治療薬の検討 (2012)
  • Author(s): 森秀一, 久保幸穂, 岸雅彦, 小西哲郎, 重本和宏
  • Organizer: 第53回日本神経学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2012-05-25
• [Presentation] Distinct mechanisms between divalent and monovalent MuSK antibodies involved with dysfunction of MuSK leading to myasthenia gravis (2011)
  • Author(s): Mori S, Kubo S, Yamada S, Miyazaki T, Shigemoto K.
  • Organizer: Society for Neuroscience
  • Place of Presentation: Washington, D.C.
  • Year and Date: 20111112-16
• [Presentation] サルコペニアのメカニズム解明に向けて (2011)
  • Author(s): 重本和宏
  • Organizer: 第33回日本基礎老化学会シンポジウム
  • Place of Presentation: 野田
  • Year and Date: 20111008-09
• [Presentation] MuSKとDok-7の相互作用は神経筋シナプスの維持に重要である (2011)
  • Author(s): 森秀一, 重本和宏
  • Organizer: 第66回日本体力医学会大会
  • Place of Presentation: 下関
  • Year and Date: 2011-09-17
• [Presentation] Distinct mechanisms between divalent and monovalent MuSK antibodies involved with dysfunction of MuSK leading to myasthenia gravis (2011)
  • Author(s): Mori S, Kubo S, Yamada S, Miyazaki T, Shigemoto K.
  • Organizer: 第34回日本神経科学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2011-09-12
• [Presentation] Complement activation is dispensable for myasthenia gravis caused by MuSK antibodies (2010)
  • Author(s): Shigemoto K, Mori S, Kubo S, Akiyoshi T, Yamada S, Miyazaki T.
  • Organizer: 10^<th> International Congress of Neuroimmunology 2010
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 20100000
• [Presentation] Strategy to treatment of myasthenia gravis caused by MuSK antibodies using a synchronized experimental animal model (2010)
  • Author(s): Mori S, Kubo S, Akiyoshi T, Yamada S, Miyazaki T, Shigemoto K.
  • Organizer: Society for Neuroscience 2010
  • Place of Presentation: San Diego
  • Year and Date: 2010-11-17
• [Presentation] New strategy to treatment of myasthenia gravis caused by MuSK antibodies using a synchronized experimental animal model (2010)
  • Author(s): Mori S, Kubo S, Akiyoshi T, Yamada S, Miyazaki T, Shigemoto K.
  • Organizer: 第33回神経科学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-09-03
• [Presentation] 筋は逆行性シグナルにより筋・運動神経を維持する (2010)
  • Author(s): 森秀一, 久保幸穂, 秋好沢諭, 山田茂, 宮崎剛, 重本和宏
  • Organizer: 第33回日本基礎老化学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-06-18
• [Presentation] Activation of complement is indispensable for myasthenia gravis caused by MuSK antibodies (2009)
  • Author(s): Mori S, Kubo S, Akiyoshi T, Yamada S, Miyazaki T, Shigemoto K.
  • Organizer: Society for Neuroscience 2009
  • Place of Presentation: Chicago
  • Year and Date: 2009-10-17
• [Presentation] Activation of complement is indispensable for myasthenia gravis caused by MuSK antibodies (2009)
  • Author(s): Mori S, Kubo S, Akiyoshi T, Yamada S, Shigemoto K.
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-09-19
• [Presentation] MuSKは神経筋シナプスの維持に重要である～研究モデル動物の確立～ (2009)
  • Author(s): 森秀一, 久保幸穂, 秋好沢諭, 山田茂, 宮崎剛, 重本和宏
  • Organizer: 第32回日本基礎老化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2009-06-27
• [Book] Myasthenia gravis Diseas Mechanisms and Immune Intervention-Chaper 17.The Tmmunopathogenesis of Experimental Autoimmune Myasthenia Gravis Induced by Autoantibodies against Muscle-specific kinase (2009)
  • Author(s): Shigemoto, K. Kubo, S. Mori. S. Yamada, S. Miyazaki, T. Akiyoshi, T and Maruyama, S.
  • Total Pages: 304-323
  • Publisher: Linus Publication, Inc.
• [Remarks] The Jackson Laboratory, USA
  • URL: http://jaxmice.jax.org/news/2012/Myasthenia_gravis.html
• [Remarks] The Jackson Laboratory, USA Podcast
  • URL: http://jaxmice.jax.org/multimedia/podcasts/20120524-Shigemoto.mp3
• [Remarks] 東京都健康長寿医療センター研究所老年病研究チーム運動器医学
  • URL: http://www.tmghig.jp/J_TMIG/j_research/DA33.html