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.

Ferri, A., Nencini, M., Battistini, S., Giannini, F., Siciliano, G., Casali, C., et al. (2004). Activity of protein phosphatase calcineurin is decreased in sporadic and familial amyotrophic lateral sclerosispatients. JOURNAL OF NEUROCHEMISTRY, 90(5), 1237-1242 [10.1111/j.1471-4159.2004.02588.x].

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

ROTILIO, GIUSEPPE;CARRI', MARIA TERESA
2004-09-01

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.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/10
English
Con Impact Factor ISI
Riluzole; Superoxide Dismutase; Humans; Calcineurin; Aged; Lymphocytes; Neuroprotective Agents; Nuclear Pore Complex Proteins; Blotting, Western; Aged, 80 and over; Amyotrophic Lateral Sclerosis; Adult; Case-Control Studies; Middle Aged; Female; Male
Ferri, A., Nencini, M., Battistini, S., Giannini, F., Siciliano, G., Casali, C., et al. (2004). Activity of protein phosphatase calcineurin is decreased in sporadic and familial amyotrophic lateral sclerosispatients. JOURNAL OF NEUROCHEMISTRY, 90(5), 1237-1242 [10.1111/j.1471-4159.2004.02588.x].
Ferri, A; Nencini, M; Battistini, S; Giannini, F; Siciliano, G; Casali, C; Damiano, M; Ceroni, M; Chiò, A; Rotilio, G; Carri', Mt
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/31839
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