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2014 Fiscal Year Final Research Report

Screening of a novel drug to activate the formation of neuromuscular junctions

Research Project

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Project/Area Number 24659673
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Orthopaedic surgery
Research InstitutionNagoya University

Principal Investigator

HIRATA Hitoshi  名古屋大学, 医学(系)研究科(研究院), 教授 (80173243)

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)
Project Period (FY) 2012-04-01 – 2015-03-31
Keywords再生医療 / 神経筋接合部 / drug repositioning / 神経再支配
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.

Free Research Field

手外科学

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Published: 2016-06-03  

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