title: Caspase-1 and -3 are sequentially activated in motor neuron death in Cu,Zn superoxide dismutase-mediated familial amyotrophic lateral sclerosis.
abstract: 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.
authors.affiliation: Massachusetts General Hospital-East, Charlestown, MA 02129, USA.
authors.forename: P
authors.initials: P
authors.lastname: Pasinelli
authors.forename: M K
authors.initials: MK
authors.lastname: Houseweart
authors.forename: R H
authors.initials: RH
authors.lastname: Brown
authors.forename: D W
authors.initials: DW
authors.lastname: Cleveland
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics; D000818:Animals; D020170:Caspase 1 / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death; D004789:Enzyme Activation; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D051379:Mice; D008854:Microscopy, Electron; D009046:Motor Neurons / Q000201:enzymology / Q000473:pathology*; D013116:Spinal Cord / Q000201:enzymology / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D013482:Superoxide Dismutase; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1