PLoS ONE (Jan 2013)

Neurotoxicity of prion peptides mimicking the central domain of the cellular prion protein.

  • Silvia Vilches,
  • Cristina Vergara,
  • Oriol Nicolás,
  • Gloria Sanclimens,
  • Sandra Merino,
  • Sonia Varón,
  • Gerardo A Acosta,
  • Fernando Albericio,
  • Miriam Royo,
  • José A Del Río,
  • Rosalina Gavín

DOI
https://doi.org/10.1371/journal.pone.0070881
Journal volume & issue
Vol. 8, no. 8
p. e70881

Abstract

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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.