Hijacking PrP(c)-dependent signal transduction: when prions impair Aβ clearance

Front Aging Neurosci. 2014 Feb 28:6:25. doi: 10.3389/fnagi.2014.00025. eCollection 2014.

Abstract

The cellular prion protein PrP(c) is the normal counterpart of the scrapie prion protein PrP (Sc), the main component of the infectious agent of transmissible spongiform encephalopathies. The recent discovery that PrP (c) can serve as a receptor for the amyloid beta (Aβ) peptide and relay its neurotoxicity is sparking renewed interest on this protein and its involvement in signal transduction processes. Disease-associated PrP (Sc) shares with Aβ the ability to hijack PrP (c)-dependent signaling cascades, and thereby instigate pathogenic events. Among these is an impairment of Aβ clearance, uncovered in prion-infected neuronal cells. These findings add another facet to the intricate interplay between PrP (c) and Aβ. Here, we summarize the connection between PrP-mediated signaling and Aβ clearance and discuss its pathological implications.

Keywords: Alzheimer’s disease; Aβ clearance; cellular prion protein; prion infection; signal transduction.

Publication types

  • Review