Amyloid-beta (Abeta) affects cellular functions leading to neurodegeneration and memory impairment via critical signal transduction processes, including also the ERK1/2 pathway. We used fibroblasts from Alzheimer’s disease (AD) patients and age-related controls to investigate possible alterations of MAPK-pathway associated to the various stages of disease that might be helpful to clarify any molecular mechanisms involved in this systemic pathology. Phosphorylated p38- and JNK-MAPK were observed in fibroblasts from MCI (mild cognitive impairment) subjects, AD patients and in oligomeric-Abeta treated cells from healthy subjects, without any correlation with disease severity. On the other hand, ERK1/2 phosphorylation was reduced in fibroblasts from mild and moderate AD, compared to severe AD patients. Also in Abeta-treated fibroblasts from control subjects, a similar decrease was shown. In MCI subjects, a trend to phospho-ERK1/2 decrease was observed too. A specific correlation was demonstrated between ERK1/2 phosphorylation and disease severity.When the four converter-MCI cases were considered, the statistical significance is improved and correlation is confirmed. Moreover, ERK phosphorylation has been involved in hyper-phosphorylation of tau, which is evident before deposition of Abeta fibrils, through the activation of p70S6-kinase. In addition, we show that the ERK pathway is specifically involved in EAAT1 molecular translation, modulating its promoter and thus impairing glutamate transport, as described in fibroblasts from AD patients. These results suggest that the ERK signaling could be of great importance for the study of the pathogenesis and the disease severity, and to investigate new treatments in AD

Zoia, C., Compagnoni, P., Ulisse, A., Verga, E., Cereda, D., Conti, E., et al. (2015). Modulation of mapk phosphorylation in fibroblasts from alzheimer patients: erk involvment in glutamate transport and tau hyperphosporylation. In Riunione Scientifica NeuroMi.

Modulation of mapk phosphorylation in fibroblasts from alzheimer patients: erk involvment in glutamate transport and tau hyperphosporylation

ZOIA, CHIARA PAOLA
Primo
;
CEREDA, DILETTA;CONTI, ELISA;TREMOLIZZO, LUCIO;ISELLA, VALERIA
Penultimo
;
FERRARESE, CARLO
Ultimo
2015

Abstract

Amyloid-beta (Abeta) affects cellular functions leading to neurodegeneration and memory impairment via critical signal transduction processes, including also the ERK1/2 pathway. We used fibroblasts from Alzheimer’s disease (AD) patients and age-related controls to investigate possible alterations of MAPK-pathway associated to the various stages of disease that might be helpful to clarify any molecular mechanisms involved in this systemic pathology. Phosphorylated p38- and JNK-MAPK were observed in fibroblasts from MCI (mild cognitive impairment) subjects, AD patients and in oligomeric-Abeta treated cells from healthy subjects, without any correlation with disease severity. On the other hand, ERK1/2 phosphorylation was reduced in fibroblasts from mild and moderate AD, compared to severe AD patients. Also in Abeta-treated fibroblasts from control subjects, a similar decrease was shown. In MCI subjects, a trend to phospho-ERK1/2 decrease was observed too. A specific correlation was demonstrated between ERK1/2 phosphorylation and disease severity.When the four converter-MCI cases were considered, the statistical significance is improved and correlation is confirmed. Moreover, ERK phosphorylation has been involved in hyper-phosphorylation of tau, which is evident before deposition of Abeta fibrils, through the activation of p70S6-kinase. In addition, we show that the ERK pathway is specifically involved in EAAT1 molecular translation, modulating its promoter and thus impairing glutamate transport, as described in fibroblasts from AD patients. These results suggest that the ERK signaling could be of great importance for the study of the pathogenesis and the disease severity, and to investigate new treatments in AD
No
abstract + poster
Scientifica
ERK, SAPKinase, TAU, Alzheimer, glutamate transporter
English
Riunione Scientifica NeuroMi
Zoia, C., Compagnoni, P., Ulisse, A., Verga, E., Cereda, D., Conti, E., et al. (2015). Modulation of mapk phosphorylation in fibroblasts from alzheimer patients: erk involvment in glutamate transport and tau hyperphosporylation. In Riunione Scientifica NeuroMi.
Zoia, C; Compagnoni, P; Ulisse, A; Verga, E; Cereda, D; Conti, E; Tremolizzo, L; Isella, V; Ferrarese, C
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/141266
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