Microglia-mediated inflammation in the central nervous system is a hallmark of the pathogenesis of several neurodegenerative diseases including Alzheimer's disease. Microglial cells activation follows the deposition of amyloid beta fibrils and it is generally considered a triggering factor in the early steps of the onset of Alzheimer's disease. Although the initial engagement of microglia seems to play a neuroprotective role, many lines of evidence indicate that a persistent activation with the production of pro-inflammatory molecules contributes to dismantle neuronal activity and to induce neuronal loss occurring in neurodegenerative diseases. To date, limited proteomic data are available on activated microglial cells in response to extracellular amyloidogenic peptides. In this study, murine microglial cells have been employed to investigate the effects of amyloid beta peptides in triggering microglial activation. The response was monitored at the proteome level through a two-dimensional gel electrophoresis based approach. Results show only a limited number of differentially expressed proteins, among these a more acidic species of the cytosolic actin, and the 14-3-3 protein, found significantly up-regulated in A-activated cells. 14-3-3 belongs to a regulatory protein family involved in important cellular processes, including those leading to neurodegenerative diseases, and thus its increased expression suggests a role of this protein in tuning microglia activation.

Calcium binding promotes prion protein fragment 90–231 conformational change toward a membrane destabilizing and cytotoxic structure / S. Sorrentino, T. Bucciarelli, A. Corsaro, A. Tosatto, S. Thellung, V. Villa, M.E. Schininà, B. Maras, R. Galeno, L. Scotti, F. Creati, A. Marrone, N. Re, A. Aceto, T. Florio, M. Mazzanti. - In: PLOS ONE. - ISSN 1932-6203. - 7:7(2012), pp. e38314.e38314.1-e38314.e38314.15.

Calcium binding promotes prion protein fragment 90–231 conformational change toward a membrane destabilizing and cytotoxic structure

M. Mazzanti
2012

Abstract

Microglia-mediated inflammation in the central nervous system is a hallmark of the pathogenesis of several neurodegenerative diseases including Alzheimer's disease. Microglial cells activation follows the deposition of amyloid beta fibrils and it is generally considered a triggering factor in the early steps of the onset of Alzheimer's disease. Although the initial engagement of microglia seems to play a neuroprotective role, many lines of evidence indicate that a persistent activation with the production of pro-inflammatory molecules contributes to dismantle neuronal activity and to induce neuronal loss occurring in neurodegenerative diseases. To date, limited proteomic data are available on activated microglial cells in response to extracellular amyloidogenic peptides. In this study, murine microglial cells have been employed to investigate the effects of amyloid beta peptides in triggering microglial activation. The response was monitored at the proteome level through a two-dimensional gel electrophoresis based approach. Results show only a limited number of differentially expressed proteins, among these a more acidic species of the cytosolic actin, and the 14-3-3 protein, found significantly up-regulated in A-activated cells. 14-3-3 belongs to a regulatory protein family involved in important cellular processes, including those leading to neurodegenerative diseases, and thus its increased expression suggests a role of this protein in tuning microglia activation.
Prion Protein ; Cell Toxicity ; Membrane Permeability ; Ion Channels ; Molecular Structure
Settore BIO/09 - Fisiologia
Settore BIO/14 - Farmacologia
2012
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/202538
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