Neurotoxicity of Prion Peptides Mimicking the Central Domain of the Cellular Prion Protein

The physiological functions of PrP(C) 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...

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Detalles Bibliográficos
Autores principales: Vilches, Silvia, Vergara, Cristina, Nicolás, Oriol, Sanclimens, Gloria, Merino, Sandra, Varón, Sonia, Acosta, Gerardo A., Albericio, Fernando, Royo, Miriam, Río, José A. Del, Gavín, Rosalina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733940/
https://www.ncbi.nlm.nih.gov/pubmed/23940658
http://dx.doi.org/10.1371/journal.pone.0070881
Descripción
Sumario:The physiological functions of PrP(C) 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 PrP(C) 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.

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