Activity of protein phosphatase calcineurin is decreased in sporadic and familial amyotrophic lateral sclerosis patients

Alberto Ferri, Monica Nencini, Stefania Battistini, Fabio Giannini, Gabriele Siciliano, Carlo Casali, Maria G. Damiano, Mauro Ceroni, Adriano Chiò, Giuseppe Rotilio, Maria Teresa Carrì

Research output: Contribution to journalArticlepeer-review

Abstract

Calcineurin (CaN) is a Ser/Thr protein phosphatase involved in a wide range of cellular responses to calcium mobilizing signals. Previous evidence supports the notion that calcineurin is oxidatively inhibited by mutant Cu, Zn superoxide dismutase (SOD1) typical of familial ALS patients in vitro and in transgenic mice. We report that calcineurin activity is markedly inhibited in lymphocytes from 37 sporadic, eight familial ALS patients and an asymptomatic subject carrying an SOD1 mutation as compared to 28 healthy controls. Two other healthy subjects, heterozygous for the D90A mutation from a recessive pedigree, have normal calcineurin activity. Immunoreactive CaN protein, age, sex and riluzole treatment are not related to calcineurin activity in samples from patients. However, we have observed a marked increase in total protein oxidation in extracts from ALS lymphocytes, as compared to extracts from control subjects. These data confirm that modification of calcineurin activity and possibly of calcineurin-mediated pathways of signal transduction (including modulation of apoptotic neuronal death) may contribute to the pathogenesis of ALS.

Original languageEnglish
Pages (from-to)1237-1242
Number of pages6
JournalJournal of Neurochemistry
Volume90
Issue number5
DOIs
Publication statusPublished - Sep 2004

Keywords

  • Amyotrophic lateral sclerosis
  • Calcineurin
  • Reactive oxygen species
  • Superoxide dimutase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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