Superoxide dismutase mutations of familial amyotrophic lateral sclerosis and the oxidative inactivation of calcineurin

Approximately 10% of all familial cases of amyotrophic lateral sclerosis (f ALS) are linked to mutations in the SOD1 gene, which encodes the copper/zin c superoxide dismutase (CuZnSOD). Recently, wild-type CuZnSOD was shown to protect calcineurin, a calcium/calmodulin-regulated phosphoprotein phosphat ase, from inactivation by reactive oxygen species. We asked whether the pro tective effect of CuZnSOD on calcineurin is affected by mutations associate d 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 i nactivation of calcineurin by different SOD mutants correlates with the sev erity of the phenotype associated with the different mutations, suggesting a potential role for calcineurin-SOD1 interaction in the etiology of fALS. (C) 2001 Federation of European Biochemical Societies. Published by Elsevie r Science B.V. All rights reserved.