title: Hijacking PrP(c)-dependent signal transduction: when prions impair Aβ clearance.
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.
authors.affiliation: INSERM UMR-S1124 Paris, France ; Sorbonne Paris Cité, UMR-S1124, Université Paris Descartes Paris, France ; Université Paris Sud 11, ED419 Biosigne Orsay, France.
authors.forename: Julia
authors.initials: J
authors.lastname: Hernandez-Rapp
authors.affiliation: INSERM UMR-S1124 Paris, France ; Sorbonne Paris Cité, UMR-S1124, Université Paris Descartes Paris, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Martin-Lannerée
authors.affiliation: INSERM UMR-S1124 Paris, France ; Sorbonne Paris Cité, UMR-S1124, Université Paris Descartes Paris, France.
authors.forename: Théo Z
authors.initials: TZ
authors.lastname: Hirsch
authors.affiliation: AP-HP Service de Biochimie, Fondation FondaMental, INSERM U942 H ôpital Lariboisière Paris, France ; Pharma Research Department, F. Hoffmann-La-Roche Ltd. Basel, Switzerland.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Launay
authors.affiliation: INSERM UMR-S1124 Paris, France ; Sorbonne Paris Cité, UMR-S1124, Université Paris Descartes Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Mouillet-Richard
keywords: Alzheimer’s disease; Aβ clearance; cellular prion protein; prion infection; signal transduction