MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice

AH Williams, G Valdez, V Moresi, X Qi, J McAnally… - Science, 2009 - science.org
AH Williams, G Valdez, V Moresi, X Qi, J McAnally, JL Elliott, R Bassel-Duby, JR Sanes
Science, 2009science.org
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 …
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.
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