肌萎缩侧索硬化
SOD1
肌肉萎缩
骨骼肌
医学
腓肠肌
转基因小鼠
超氧化物歧化酶
去神经支配
神经肌肉接头
内科学
内分泌学
进行性肌萎缩
转基因
病理
生物
神经科学
疾病
氧化应激
生物化学
基因
作者
Yuki Nagahara,Masamitsu Shimazawa,Hirotaka Tanaka,Yoko Ono,Yoichi Noda,Kazuki Ohuchi,Kazuhiro Tsuruma,Masahisa Katsuno,Gen Sobue,Hideaki Hara
摘要
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons and subsequent muscular atrophy. The quality of life of patients with ALS is significantly improved by ameliorating muscular symptoms. We previously reported that glycoprotein nonmetastatic melanoma protein B (GPNMB; osteoactivin) might serve as a target for ALS therapy. In the present study, superoxide dismutase 1/glycine residue 93 changed to alanine (SOD1 G93A ) transgenic mice were used as a model of ALS. Expression of the C‐terminal fragment of GPNMB was increased in the skeletal muscles of SOD1 G93A mice and patients with sporadic ALS. SOD1 G93A /GPNMB transgenic mice were generated to determine whether GPNMB expression ameliorates muscular symptoms. The weight and cross‐sectional area of the gastrocnemius muscle, number and cross‐sectional area of myofibers, and denervation of neuromuscular junctions were ameliorated in SOD1 G93A /GPNMB vs. SOD1 G93A mice. Furthermore, direct injection of a GPNMB expression plasmid into the gastrocnemius muscle of SOD1 G93A mice increased the numbers of myofibers and prevented myofiber atrophy. These findings suggest that GPNMB directly affects skeletal muscle and prevents muscular pathology in SOD1 G93A mice and may therefore serve as a target for therapy of ALS. © 2015 Wiley Periodicals, Inc.
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