Mitochondrial defects contribute to impaired translational in SMA motor neurons

Spinal muscular atrophy (SMA) is a neuromuscular disease, characterized by loss of lower alpha motoneurons, which leads to proximal muscle weakness. SMA is caused by reduced levels of Survival of Motor Neuron protein due to biallelic deletions or mutations in the SMN1 gene. Dysfunctional mitochondria can harm cells by decreased ATP production, but also by increased oxidative stress due to elevated production of reactive oxygen species (ROS). In this study, whole proteome analysis was performed using the Taiwanese SMA mouse model on an FVB/N background to identify changes in the proteome related to oxidative stress. Therefore, primary WT and SMA motoneurons were treated with a known anti-oxidant N-Acetylcysteine, the ROS inducer menadione and the cell culture supplement sodium pyruvate. Furthermore, this study aims to investigate changes in mRNA translation initiation affected by oxidative stress in SMA.