title: Superoxide dismutase mutations of familial amyotrophic lateral sclerosis and the oxidative inactivation of calcineurin.
abstract: Approximately 10% of all familial cases of amyotrophic lateral sclerosis (fALS) are linked to mutations in the SOD1 gene, which encodes the copper/zinc superoxide dismutase (CuZnSOD). Recently, wild-type CuZnSOD was shown to protect calcineurin, a calcium/calmodulin-regulated phosphoprotein phosphatase, from inactivation by reactive oxygen species. We asked whether the protective effect of CuZnSOD on calcineurin is affected by mutations associated with fALS. For this, we monitored calcineurin activity in the presence of mutant and wild-type SOD. We found that the degree of protection against inactivation of calcineurin by different SOD mutants correlates with the severity of the phenotype associated with the different mutations, suggesting a potential role for calcineurin-SOD1 interaction in the etiology of fALS.
authors.affiliation: Department of Neurology, University of Ulm, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Volkel
authors.forename: M
authors.initials: M
authors.lastname: Scholz
authors.forename: J
authors.initials: J
authors.lastname: Link
authors.forename: M
authors.initials: M
authors.lastname: Selzle
authors.forename: P
authors.initials: P
authors.lastname: Werner
authors.forename: R
authors.initials: R
authors.lastname: Tunnemann
authors.forename: G
authors.initials: G
authors.lastname: Jung
authors.forename: A C
authors.initials: AC
authors.lastname: Ludolph
authors.forename: A
authors.initials: A
authors.lastname: Reuter
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D019703:Calcineurin / Q000737:chemistry / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D002417:Cattle; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009154:Mutation; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: D065095:Calcineurin Inhibitors; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D019703:Calcineurin