Abstract:

Spinal muscular atrophy (SMA) is a hereditary pediatric motor neuron (MN) disease: survival motor neuron 1 (SMN1) gene mutation determines MN degeneration and, consequently, muscle atrophy, breathing and swallowing difficulties, and, in the most severe cases, premature death. A second unaffected gene (SMN2) is present, but it can only produce a limited amount of functional protein, modulating the disease severity and progression. SMN, ubiquitously expressed, is mainly involved in the assembly of small nuclear ribonucleoproteins and pre-mRNA splicing requirements (Lunn and Wang, 2008). Its reduction determines selective MN loss: the type of cell death leading to neurodegeneration remains debated, since evidence of both increased apoptosis and dysregulated autophagy have been reported in SMA.