Open AccessMechanisms of Muscle Denervation in Aging: Insights from a Mouse Model of Amyotrophic Lateral Sclerosis
Author(s) -
Kevin H.J. Park
Publication year - 2015
Publication title -
aging and disease
Language(s) - English
Resource type - Journals
ISSN - 2152-5250
DOI - 10.14336/ad.2015.0506
Subject(s) - denervation , amyotrophic lateral sclerosis , neuromuscular junction , sod1 , neuroscience , myogenin , context (archaeology) , biology , muscle weakness , genetically modified mouse , microbiology and biotechnology , medicine , transgene , endocrinology , anatomy , myocyte , gene , genetics , myogenesis , disease , paleontology
Muscle denervation at the neuromuscular junction (NMJ) is thought to be a contributing factor in age-related muscle weakness. Therefore, understanding the mechanisms that modulate NMJ innervation is a key to developing therapies to combat age-related muscle weakness affecting the elderly. Two mouse models, one lacking the Cu/Zn superoxide dismutase (SOD1) gene and another harboring the transgenic mutant human SOD1 gene, display progressive changes at the NMJ, including muscle endplate fragmentation, nerve terminal sprouting, and denervation. These changes at the NMJ share many of the common features observed in the NMJs of aged mice. In this review, research findings demonstrating the effects of PGC-1α, IGF-1, GDNF, MyoD, myogenin, and miR-206 on NMJ innervation patterns in the G93A SOD1 mice will be highlighted in the context of age-related muscle denervation.