Journal Article

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

Williams, Andrew H, Bassel-Duby, Rhonda, Olson, Eric N, Qi, Xiaoxia, Valdez, Gregorio, McAnally, John, Sanes, Joshua R, Moresi, Viviana, Elliott, Jeffrey L

2009

Overview

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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Amyotrophic lateral sclerosis / Amyotrophic Lateral Sclerosis - pathology / Amyotrophic Lateral Sclerosis - physiopathology / animal models / Animals / Axons - physiology / Carrier Proteins - genetics / Carrier Proteins - metabolism / Cellular biology / Denervation / disease course / Disease Models, Animal / Disease Progression / fibroblast growth factors / Fibroblast Growth Factors - metabolism / histone deacetylase / Histone Deacetylases - genetics / Histone Deacetylases - metabolism / Intercellular Signaling Peptides and Proteins / Intracellular Signaling Peptides and Proteins / Mice / Mice, Transgenic / MicroRNA / MicroRNAs - genetics / MicroRNAs - metabolism / Motor neurons / Motor Neurons - pathology / Motor Neurons - physiology / Muscle Denervation / Muscle, Skeletal - innervation / Muscle, Skeletal - metabolism / Muscle, Skeletal - pathology / Muscles / muscular atrophy / Muscular system / MyoD Protein - genetics / MyoD Protein - metabolism / Myogenin - genetics / Myogenin - metabolism / myotubes / Nerve Regeneration / nerve tissue / Nerves / Neuromuscular Junction - growth & development / Neuromuscular Junction - pathology / Neuromuscular Junction - physiology / Neurons / paralysis / pathogenesis / Ribonucleic acid / RNA / RNA Interference / Rodents / Signal Transduction / Skeletal muscle / synapse / Synapses / T tests / Transcriptional Activation / Up regulation