2005 Fiscal Year Final Research Report Summary
Analysis of myasthenic disease caused by MuSK dysfunction
| Project/Area Number |
16590831
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Ehime University |
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Principal Investigator |
SHIGEMOTO Kazuhiro Ehime Univ., School of Med., Associate Professor, 医学部, 助教授 (40284400)
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| Co-Investigator(Kenkyū-buntansha) |
MOMINOKI Katsumi Ehime University, Integrated Center for Sciences, Lecturer, 総合科学研究支援センター, 講師 (70304615)
MATSUDA Seiji Ehime University, School of Medicine, Professor, 医学部, 教授 (40173843)
MARUYAMA Naoki Tokyo Metropolitan Institute of Gerontology, Organ Disorder and Aging Research Group Division of Physiology and Aging, Vice director, 加齢臓器障害研究グループ, 副所長 (00115940)
KUBO Sachiho Tokyo Metropolitan Institute of Gerontology, Organ Disorder and Aging Research Group Division of Physiology and Aging, Research associates, 加齢臓器障害研究グループ, 助手 (00280769)
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| Project Period (FY) |
2004 – 2005
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| Keywords | muscle-speficik kinase / myasthenia gravis / AChR / neuromusclar junction |
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| Research Abstract |
Muscle-specific kinase (MuSK) is critical for the synaptic clustering of nicotinic acetylcholine receptors (AChR) and plays multiple roles in the organization and maintenance of neuromuscular junctions (NMJ). MuSK is activated by agrin, which is released from motoneurons, and induces AChR clustering at the postsynaptic membrane. Although autoantibodies against the ectodomain of MuSK have been found in a proportion of patients with generalized myasthenia gravis (MG), it is unclear whether MuSK autoantibodies are the causative agent of generalized MG. In the present study, rabbits immunized with MuSK ectodomain protein manifested MG-like muscle weakness with a reduction of AChR clustering at the NMJ. The autoantibodies activated MuSK and blocked AChR clustering induced by agrin or by mediators that do not activate MuSK. Thus, MuSK autoantibodies rigorously inhibit AChR clustering mediated by multiple pathways, an outcome that broadens our general comprehension of the pathogenesis of MG.
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