Hijacking PrPc-dependent signal transduction: when prions impair Aβ clearance

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