In vitro and in vivo experiments demonstrate that motor neuron death depends on sequential activation of caspase-1 and caspase-3 in familial ALS with mutant SOD1. Increased oxidative stress caused by mutant SOD1 leads to activation of caspase-1, resulting in caspase-3-dependent axonal loss and apoptotic cell death of motor neurons in the spinal cord and cortex [217]. This evidence concerns the gene CASP3 and amyotrophic lateral sclerosis.