Spinal muscular atrophy (SMA) is an autosomal recessively inherited motor neuron disease that causes alpha motor neuron degeneration in the spinal cord, symmetrical muscle weakness, and atrophy. SMA is caused by mutations in the survival of motor neuron 1 (SMN1) gene, which results in a reduced amount of survival motor neuron (SMN) protein synthesis. Although there have been many studies investigating SMA pathogenesis, the mechanism by which the reduced SMN protein levels cause motor neuron degeneration and muscle atrophy is unclear. Generally, muscle weakness is considered a secondary outcome of motor neuron degeneration in SMA. However, recent studies have shown that intrinsic skeletal muscle defects contribute to SMA pathogenesis and targeting skeletal muscle might be beneficial as a potential therapy approach. This paper aims to review the recent findings on the role of skeletal muscle in SMA pathogenesis.
Key words: Spinal muscular atrophy, SMN, muscle atrophy, skeletal muscle