Glycoprotein nonmetastatic melanoma protein B ameliorates skeletal muscle lesions in a SOD1G93A mouse model of amyotrophic lateral sclerosis |
| |
Authors: | Yuki Nagahara Masamitsu Shimazawa Hirotaka Tanaka Yoko Ono Yasuhiro Noda Kazuki Ohuchi Kazuhiro Tsuruma Masahisa Katsuno Gen Sobue Hideaki Hara |
| |
Institution: | 1. Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan;2. Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan |
| |
Abstract: | 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 (SOD1G93A) transgenic mice were used as a model of ALS. Expression of the C‐terminal fragment of GPNMB was increased in the skeletal muscles of SOD1G93A mice and patients with sporadic ALS. SOD1G93A/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 SOD1G93A/GPNMB vs. SOD1G93A mice. Furthermore, direct injection of a GPNMB expression plasmid into the gastrocnemius muscle of SOD1G93A mice increased the numbers of myofibers and prevented myofiber atrophy. These findings suggest that GPNMB directly affects skeletal muscle and prevents muscular pathology in SOD1G93A mice and may therefore serve as a target for therapy of ALS. © 2015 Wiley Periodicals, Inc. |
| |
Keywords: | glycoprotein nonmetastatic melanoma protein B GPNMB amyotrophic lateral sclerosis ALS skeletal muscle neuromuscular junction transgenic mouse sporadic ALS |
|
|