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

444 Citations (Scopus)

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

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Amyotrophic Lateral Sclerosis
MicroRNAs
Synapses
Regeneration
Motor Neurons
Fibroblast Growth Factor 4
Muscle Denervation
Histone Deacetylases
Muscular Atrophy
Skeletal Muscle Fibers
Wounds and Injuries
Paralysis
Neurodegenerative Diseases
Disease Progression
Skeletal Muscle

ASJC Scopus subject areas

  • General

Cite this

MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice. / Williams, Andrew H.; Valdez, Gregorio; Moresi, Viviana; Qi, Xiaoxia; McAnally, John; Elliott, Jeffrey L.; Bassel-Duby, Rhonda; Sanes, Joshua R.; Olson, Eric N.

In: Science, Vol. 326, No. 5959, 11.12.2009, p. 1549-1554.

Research output: Contribution to journalArticle

Williams, Andrew H. ; Valdez, Gregorio ; Moresi, Viviana ; Qi, Xiaoxia ; McAnally, John ; Elliott, Jeffrey L. ; Bassel-Duby, Rhonda ; Sanes, Joshua R. ; Olson, Eric N. / MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice. In: Science. 2009 ; Vol. 326, No. 5959. pp. 1549-1554.
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