title: PrP(C) signalling in neurons: from basics to clinical challenges.
abstract: The cellular prion protein PrP(C) was identified over twenty-five years ago as the normal counterpart of the scrapie prion protein PrP(Sc), itself the main if not the sole component of the infectious agent at the root of Transmissible Spongiform Encephalopathies (TSEs). PrP(C) is a ubiquitous cell surface protein, abundantly expressed in neurons, which constitute the targets of PrP(Sc)-mediated toxicity. Converging evidence have highlighted that neuronal, GPI-anchored PrP(C) is absolutely required for prion-induced neuropathogenesis, which warrants investigating into the normal function exerted by PrP(C) in a neuronal context. It is now well-established that PrP(C) can serve as a cell signalling molecule, able to mobilize transduction cascades in response to interactions with partners. This function endows PrP(C) with the capacity to participate in multiple neuronal processes, ranging from survival to synaptic plasticity. A diverse array of data have allowed to shed light on how this function is corrupted by PrP(Sc). Recently, amyloid Aβ oligomers, whose accumulation is associated with Alzheimer's disease (AD), were shown to similarly instigate toxic events by deviating PrP(C)-mediated signalling. Here, we provide an overview of the various signal transduction cascades ascribed to PrP(C) in neurons, summarize how their subversion by PrP(Sc) or Aβ oligomers contributes to TSE or AD neuropathogenesis and discuss the ensuing clinical implications.
authors: INSERM UMR-S1124, 75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMR-S1124, 75006 Paris, France.
authors: Théo Z
authors: TZ
authors: Hirsch
authors: INSERM UMR-S1124, 75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMR-S1124, 75006 Paris, France; Université Paris Sud 11, ED419 Biosigne, 91400 Orsay, France.
authors: Julia
authors: J
authors: Hernandez-Rapp
authors: INSERM UMR-S1124, 75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMR-S1124, 75006 Paris, France.
authors: Séverine
authors: S
authors: Martin-Lannerée
authors: AP-HP Service de Biochimie, Fondation FondaMental, INSERM U942 Hôpital Lariboisière, 75010 Paris, France; Pharma Research Department, F. Hoffmann-La-Roche Ltd., CH-4070 Basel, Switzerland.
authors: Jean-Marie
authors: JM
authors: Launay
authors: INSERM UMR-S1124, 75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMR-S1124, 75006 Paris, France. Electronic address: sophie.mouillet-richard@parisdescartes.fr.
authors: Sophie
authors: S
authors: Mouillet-Richard
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000166:cytology* / Q000473:pathology; D018621:PrPC Proteins / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D018621:PrPC Proteins; D017981:Receptors, Neurotransmitter
keywords: Alzheimer's disease; Aβ; Cell signalling; Neurons; Prion diseases; Prion protein