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 sclerosis patients. 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 sclerosis patients
BATTISTINI S.;GIANNINI F.;
2004-01-01
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.File | Dimensione | Formato | |
---|---|---|---|
Calcineurin.pdf
non disponibili
Tipologia:
Post-print
Licenza:
NON PUBBLICO - Accesso privato/ristretto
Dimensione
143.48 kB
Formato
Adobe PDF
|
143.48 kB | Adobe PDF | Visualizza/Apri Richiedi una copia |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/11365/3264
Attenzione
Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo