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
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