Development of an inhibitory peptide for myostatin: its implications for muscular dystrophy and sarcopenia
| Project/Area Number |
26461285
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
Yutaka Ohsawa 川崎医科大学, 医学部, 講師 (80246511)
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| Co-Investigator(Kenkyū-buntansha) |
西松 伸一郎 川崎医科大学, 医学部, 准教授 (20222185)
村上 龍文 川崎医科大学, 医学部, 准教授 (30330591)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 筋ジストロフィー / サルコペニア / マイオスタチン / 再生医療 / 筋萎縮 |
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| Outline of Final Research Achievements |
Myostatin, a muscle-specific transforming growth factor-beta, negatively regulates skeletal muscle mass. The N-terminal prodomain of myostatin noncovalently binds to and suppresses the C-terminal mature domain (ligand) as an inactive circulating complex. Here, we identified the inhibitory core (IC) region that inhibited myostatin-induced transcriptional activity by 79% compared with the full-length prodomain. We found that the IC suppresses not only the ligand, but also prevents two distinct membrane receptors from binding to the ligand. Indeed, the IC inhibits myostatin, but not TGF-beta 1, and activin. Local injection of the IC peptide ameliorates muscle atrophy in a rodent model of muscular dystrophy (Ohsawa, et al. PLoS One 10:e0133713 2015,, 2015).
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Report
(3 results)
Research Products
(14 results)
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[Journal Article] Identification of the minimum peptide from mouse myostatin prodomain for human myostatin inhibition.2015
Author(s)
Takayama K, Noguchi Y, Aoki S, Takayama S, Yoshida M, Asari T, Yakushiji F, Nishimatsu S, Ohsawa Y, Itoh F, Negishi Y, Sunada Y, Hayashi Y
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Journal Title
J Med Chem
Volume: 58
Issue: 3
Pages: 1544-1549
DOI
Related Report
Peer Reviewed
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[Journal Article] The Inhibitory Core of the Myostatin Prodomain: Its Interaction with Both Type I and II Membrane Receptors, and Potential to Treat Muscle Atrophy.2015
Author(s)
Ohsawa Y, Takayama K, Nishimatsu S, Okada T, Fujino M, Fukai Y, Murakami T, Hagiwara H, Itoh F, Tsuchida K, Hayashi Y, Sunada Y.
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Journal Title
PLoS One
Volume: 10
Issue: 7
Pages: e0133713-e0133713
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] 筋ジストロフィー関連疾患における TGF-βシグナルの解明と標的医薬の開発2015
Author(s)
大澤 裕, 深井雄太, 藤野雅広, 西松伸一郎, 高山健太郎, 伊東史子, 林 良雄, 土田邦博, 砂田芳秀
Organizer
平成２７年度「筋ジストロフィー関連疾患の基盤的診断・治療開発研究」(26-8) 西野班 班会議
Place of Presentation
国立研究開発法人 国立精神・神経医療研究センター 教育研修棟 1Ｆ ユニバーサルホール(東京都・小平市)
Year and Date
2015-12-07
Related Report
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