NR ASWT
AU Gavin,R.; Braun,N.; Nicolas,O.; Parra,B.; Urena,J.M.; Mingorance,A.; Soriano,E.; Torres,J.M.; Aguzzi,A.; del Rio,J.A.
TI PrP(106-126) activates neuronal intracellular kinases and Egr1 synthesis through activation of NADPH-oxidase independently of PrPc
QU FEBS Letters 2005 Aug 1; 579(19): 4099-106
PT journal article
AB 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.
MH Animals; DNA-Binding Proteins/*biosynthesis; Enzyme Activation; Female; Glycogen Synthase Kinases/metabolism; Immediate-Early Proteins/*biosynthesis; Immunohistochemistry; Mice; Mitogen-Activated Protein Kinases/*metabolism; NADPH Oxidase/*metabolism; Neurons/*enzymology; Peptide Fragments/*physiology; PrPc Proteins/*physiology; Pregnancy; Prions/*physiology; Reactive Oxygen Species; Research Support, Non-U.S. Gov't; Transcription Factors/*biosynthesis; tau Proteins/metabolism
AD Development and Regeneration of the CNS, Department of Cell Biology, Barcelona Science Park - IRB, University of Barcelona, Spain.
SP englisch
PO Niederlande