MicroRNA-206 Delays ALS Progression and Promotes Regeneration of Neuromuscular Synapses in Mice

Abstract

An Innervative Small RNA Amyotrophic lateral sclerosis (ALS) is a relentless disease characterized by progressive degeneration of motor neurons that control muscle movement, leading to muscle atrophy and paralysis. Williams et al. (p. 1549 ; see the Perspective by Brown ) show that a small noncoding RNA that is selectively expressed in skeletal muscle, miR-206, senses motor neuron injury or loss and helps ameliorate resultant muscle damage by promoting regeneration of neuromuscular synapses. Expression of miR-206 was dramatically induced in a mouse model of ALS, and when this RNA was removed from mice by genetic manipulation, the disease progressed at a faster rate. The salutary effects of miR-206 appear to be mediated through a signaling pathway in muscle cells involving histone deacetylase 4 and a fibro-blast growth factor modulator, activation of which leads to release of factors that promote nerve-muscle interactions.