MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by loss of motor neurons, denervation of target muscles, muscle atrophy, and paralysis. Understanding ALS pathogenesis may require a fuller understanding of the bidirectional signaling between motor neurons and skeletal muscle fibers at neuromuscular synapses. Here, we show that a key regulator of this signaling is miR-206, a skeletal muscle-specific microRNA that is dramatically induced in a mouse model of ALS. Mice that are genetically deficient in miR-206 form normal neuromuscular synapses during development, but deficiency of miR-206 in the ALS mouse model accelerates disease progression. miR-206 is required for efficient regeneration of neuromuscular synapses after acute nerve injury, which probably accounts for its salutary effects in ALS. miR-206 mediates these effects at least in part through histone deacetylase 4 and fibroblast growth factor signaling pathways. Thus, miR-206 slows ALS progression by sensing motor neuron injury and promoting the compensatory regeneration of neuromuscular synapses.
Pubmed ID: 20007902 RIS Download
Amyotrophic Lateral Sclerosis | Animals | Axons | Carrier Proteins | Disease Models, Animal | Disease Progression | Fibroblast Growth Factors | Histone Deacetylases | Mice | Mice, Transgenic | MicroRNAs | Motor Neurons | Muscle Denervation | Muscle, Skeletal | MyoD Protein | Myogenin | Nerve Regeneration | Neuromuscular Junction | RNA Interference | Signal Transduction | Transcriptional Activation | Up-Regulation