Elucidation of the mechanism for formation of protein aggregates in skeletal myofibers with distal myopathy with rimmed vacuoles

2014 Fiscal Year Final Research Report

• Project/Area Number: 23390236
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: NOGUCHI Satoru 独立行政法人国立精神・神経医療研究センター, 神経研究所 疾病研究第一部, 室長 (00370982)
• Co-Investigator(Kenkyū-buntansha): NISHIMURA Hiroaki 独立行政法人国立精神・神経医療研究センター, 神経研究所 疾病研究第一部, 流動研究員 (10399909) ; URUHA Akinori 独立行政法人国立精神・神経医療研究センター, トランスレーショナルメディカルセンター臨床開発部, 流動研究員 (70635078)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: 細胞・組織 / 蛋白質 / 糖 / 骨格筋 / アミロイド

Outline of Final Research Achievements

Distal myopathy with rimmed vacuoles (DMRV) is one of the protein aggregate myopathies in which numerous proteins and autophagic vacuoles were accumulated in the myofibers. The mechanism, in which the accumulation of these proteins secondarily leads to defects of muscle functions, has not been clarified. In this study, we clarified the following four results: (1) distribution of the accumulated proteins along cytoskeleton, especially microtubules in DMRV myofibers,; (2) no protein accumulation in brain tissues of DMRV model mice; (3) numerous numbers of protein inclusions in atrophic muscles leading to a remarkable weakness in the mice with skeletal muscle-specific deficiency of autophagy as a model of the related disorder; (4) the accumulation of myofibril-regulating proteins, metabolic enzymes and polyubiquitin proteins in the cytoplasmic bodies formed in skeletal muscles in Pompe disease by proteome analysis.

Free Research Field

医歯薬学