Restoration of myogenesis in ALS-myocytes through miR-26a-5p-mediated Smad4 inhibition and its impact on motor neuron development

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset paralytic disorder, characterized primarily by a progressive loss of motor neurons (MNs) in which degeneration skeletal muscle involvement has been demonstrated. Skeletal muscle is a plastic tissue that responds to insults through proliferation and differentiation of satellite cells. Skeletal muscle degeneration and regeneration are finely regulated by signals that regulate satellite cell proliferation and differentiation. It is known that satellite cell differentiation is impaired in ALS, but little is known about the involvement of microRNAs (miRNAs) and their role in intercellular communication in ALS. Here we demonstrated impaired differentiation of satellite cells derived from ALS mice related to the impairment of myogenic p38MAPK and protein kinase A (PKA)/pCREB signaling pathways that can be regulated by miR-882 and -134-5p. These miRNAs participate in autocrine signaling in association with miR-26a-5p that, secr...