title: The human G93A-superoxide dismutase-1 mutation, mitochondrial glutathione and apoptotic cell death.
abstract: Mutations in Cu/Zn superoxide dismutase are a cause of motor neuron death in about 20% of cases of familial amyotrophic lateral sclerosis (ALS). Although the molecular mechanism of which these mutations induce motor neuron cell death is to a large extent unknown, there is significant evidence that effects on mitochondrial function and development of oxidative stress make a major contribution to the selective death of motor neurons in this disease. In this overview article we review the current understanding of mutant SOD1-mediated motor neuron degeneration in ALS with focus on oxidative damage and mitochondrial dysfunction. We also present novel information on the role of mitochondrial glutathione for the survival of NSC-34 cells stably transfected with the human SOD1(G93A) mutation, putting forward the hypothesis that this antioxidant pool provides a potentially useful target for therapeutic intervention.
authors.affiliation: Centre for Neuroscience and Department of Medical Biochemistry, School of Medicine, Flinders University, GPO Box 2100, Adelaide, SA 5001, Australia. hakan.muyderman@flinders.edu.au
authors.forename: H
authors.initials: H
authors.lastname: Muyderman
authors.forename: P G
authors.initials: PG
authors.lastname: Hutson
authors.forename: D
authors.initials: D
authors.lastname: Matusica
authors.forename: M-L
authors.initials: ML
authors.lastname: Rogers
authors.forename: R A
authors.initials: RA
authors.lastname: Rush
mesh_terms: D000409:Alanine / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics*; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D016923:Cell Death / Q000235:genetics; D005978:Glutathione / Q000235:genetics* / Q000378:metabolism; D005998:Glycine / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009046:Motor Neurons / Q000201:enzymology / Q000473:pathology*; D018384:Oxidative Stress / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
chemical_list: C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D005978:Glutathione; D000409:Alanine; D005998:Glycine