Neurotoxicity of Prion Peptides Mimicking the Central Domain of the Cellular Prion Protein
Open Access
- 5 August 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (8), e70881
- https://doi.org/10.1371/journal.pone.0070881
Abstract
The physiological functions of PrPC remain enigmatic, but the central domain, comprising highly conserved regions of the protein may play an important role. Indeed, a large number of studies indicate that synthetic peptides containing residues 106–126 (CR) located in the central domain (CD, 95–133) of PrPC are neurotoxic. The central domain comprises two chemically distinct subdomains, the charge cluster (CC, 95–110) and a hydrophobic region (HR, 112–133). The aim of the present study was to establish the individual cytotoxicity of CC, HR and CD. Our results show that only the CD peptide is neurotoxic. Biochemical, Transmission Electron Microscopy and Atomic Force Microscopy experiments demonstrated that the CD peptide is able to activate caspase-3 and disrupt the cell membrane, leading to cell death.Keywords
This publication has 80 references indexed in Scilit:
- Prion Protein and Its Conformational Conversion: A Structural PerspectivePublished by Springer Nature ,2011
- Structural Properties and Dynamic Behavior of Nonfibrillar Oligomers Formed by PrP(106−126)Journal of the American Chemical Society, 2010
- Regulation of GABAA and Glutamate Receptor Expression, Synaptic Facilitation and Long-Term Potentiation in the Hippocampus of Prion Mutant MicePLOS ONE, 2009
- The Changing Face of Glucagon Fibrillation: Structural Polymorphism and Conformational ImprintingJournal of Molecular Biology, 2005
- PrP(106–126) activates neuronal intracellular kinases and Egr1 synthesis through activation of NADPH‐oxidase independently of PrPcFEBS Letters, 2005
- Anchorless Prion Protein Results in Infectious Amyloid Disease Without Clinical ScrapieScience, 2005
- In VivoandIn VitroNeurotoxicity of the Human Prion Protein (PrP) Fragment P118–135 Independently of PrP ExpressionJournal of Neuroscience, 2003
- Developmental expression of the cellular prion protein in elongating axonsEuropean Journal of Neuroscience, 2002
- Comment on: Neurotoxicity of prion peptide 106-126 not confirmed, by Beat Kunz, Erika Sandmeier, Philipp ChristenFEBS Letters, 2000
- Normal development and behaviour of mice lacking the neuronal cell-surface PrP proteinNature, 1992