What links muscle cellular pathways to ALS?
Changes to muscle cellular pathways may occur downstream of motor neuron pathology in ALS. Genetic changes to pathways that are important to muscle function may also be causal of the disease. In addition, changes to the muscle may be responsible for motor neuron death. Pathological changes occur in muscle before disease onset and independent from MN degeneration, and the muscle may release toxic elements, such as via extracellular vesicle secretion. Muscle metabolism and mitochondrial activity, RNA processing, tissue-resident stem cell function responsible for muscle regeneration, and proteostasis that regulates muscle mass in adulthood, are all deregulated in ALS. There may also be a link between motor neuron death, the immune system, and muscle cells, as muscle-resident glial cells have been shown to activate upon nerve injury. Muscle-restricted expression of a localized insulin-like growth factor Igf-1 isoform maintained muscle integrity and enhanced satellite cell activity in SOD1(G93A) transgenic mice.