| Project/Area Number |
24659673
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Nagoya University |
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Principal Investigator |
HIRATA Hitoshi 名古屋大学, 医学(系)研究科(研究院), 教授 (80173243)
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| Co-Investigator(Kenkyū-buntansha) |
KURIMOTO Shigeru 名古屋大学, 医学系研究科, 特任講師 (70597856)
OHNO Kinji 名古屋大学, 医学系研究科, 教授 (80397455)
TORIHASHI Shigeko 名古屋大学, 医学系研究科, 教授 (90112961)
MIZUSHIMA Hideyuki 名古屋大学, 医学部附属病院, 病院助教 (80718403)
夏目 唯弘 名古屋大学, 医学部附属病院, その他 (30624316)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 再生医療 / 神経筋接合部 / drug repositioning / 神経再支配 |
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| Outline of Final Research Achievements |
During the formation of neuromuscular junctions (NMJs), binding of agrin to LRP4 induces MuSK phosphorylation, which activates ATF2 downstream of JNK and induces clustering of acetylcholine receptors (AChRs). We used the drug repositioning strategy, in which a drug already used for a specific disease is applied to treat another disease, to identify an FDA-approved drug that enhances the agrin/LRP4/MuSK signaling and NMJ formation. Drug A increases MuSK phosphorylation in dose-dependent manner. In C2C12 myotubes, number of AChR clusters were increased in the presence of Drug A together with agrin.
Moreover, drug A increases the expression of AChR-e, rapsyn and Col-Q mRNAs in neurotization model mice.
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