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

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

Research output: Contribution to journalArticle

478 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1549-1554
Number of pages6
JournalScience
Volume326
Issue number5959
DOIs
StatePublished - Dec 11 2009

ASJC Scopus subject areas

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