PrP(106-126) activates neuronal intracellular kinases and Egr1 synthesis through activation of NADPH-oxidase independently of PrPc

Prion diseases are characterised by severe neural lesions linked to the presence of an abnormal protease-resistant isoform of cellular prion protein (PrPc). The peptide PrP(106-126) is widely used as a model of neurotoxicity in prion diseases. Here, we examine in detail the intracellular signalling cascades induced by PrP(106-126) in cortical neurons and the participation of PrPc. We show that PrP(106-126) induces the activation of subsets of intracellular kinases (e.g.;ERK1/2), early growth response 1 synthesis and induces caspase-3 activity, all of which are mediated by nicotinamide adenine dinucleotide phosphate hydrogen-oxidase activity and oxidative stress. However, cells lacking PrPc are similarly affected after peptide exposure, and this questions the involvement of PrPc in these effects. © 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Bibliographic Details

Main Authors:	Gavín, R., Braun, N., Nicolas, O., Parra, B., Ureña, J. M., Mingorance, A., Soriano, E., Torres, J. M., Aguzzi, A., Del Río, J. A.
Format:	journal article biblioteca
Language:	eng
Published:	2005
Online Access:	http://hdl.handle.net/20.500.12792/1688
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