Caspase-1 and-3 are sequentially activated in motor neuron death in Cu, Zn superoxide dismutase-mediated familial amyotrophic lateral sclerosis

P Pasinelli, MK Houseweart… - Proceedings of the …, 2000 - National Acad Sciences
P Pasinelli, MK Houseweart, RH Brown Jr, DW Cleveland
Proceedings of the National Academy of Sciences, 2000National Acad Sciences
Familial amyotrophic lateral sclerosis-linked mutations in copper-zinc superoxide dismutase
cause motor neuron death through one or more acquired toxic properties. An early event in
the mechanism of toxicity from such mutants is now demonstrated to be activation of
caspase-1. Neuronal death, however, follows only after months of chronic caspase-1
activation concomitantly with activation of the executioner caspase-3 as the final step in the
toxic cascade. Thus, a common toxicity of mutant SOD1 is a sequential activation of at least …
Familial amyotrophic lateral sclerosis-linked mutations in copper-zinc superoxide dismutase cause motor neuron death through one or more acquired toxic properties. An early event in the mechanism of toxicity from such mutants is now demonstrated to be activation of caspase-1. Neuronal death, however, follows only after months of chronic caspase-1 activation concomitantly with activation of the executioner caspase-3 as the final step in the toxic cascade. Thus, a common toxicity of mutant SOD1 is a sequential activation of at least two caspases, caspase-1 that acts slowly as a chronic initiator and caspase-3 acting as the final effector of cell death.
National Acad Sciences