title: Understanding the neurospecificity of Prion protein signaling.
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 (TSEs). It is a ubiquitous cell-surface glycoprotein, abundantly expressed in neurons, which constitute the targets of TSE pathogenesis. The presence of PrP(C) at the surface of neurons is an absolute requirement for the development of prion diseases and corruption of PrP(C) function(s) within an infectious context emerges as a proximal cause for PrP(Sc)-induced neurodegeneration. Experimental evidence gained over the past decade indicates that PrP(C) has the capacity to mobilize promiscuous signal transduction cascades that, notably, contribute to cell homeostasis. Beyond ubiquitous effectors, much data converge onto a neurospecificity of PrP(C) signaling, which may be the clue to neuronal cell demise in prion disorders. In this article, we highlight the requirement of PrP(C) for TSEs-associated neurodegeneration and review the current knowledge of PrP(C)-dependent signal transduction in neuronal cells and its implications for PrP(Sc)-mediated neurotoxicity.
authors.affiliation: INSERM U747, Paris Descartes University, 75006 Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Schneider
authors.forename: Mathea
authors.initials: M
authors.lastname: Pietri
authors.forename: Elodie
authors.initials: E
authors.lastname: Pradines
authors.forename: Damien
authors.initials: D
authors.lastname: Loubet
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Launay
authors.forename: Odile
authors.initials: O
authors.lastname: Kellermann
authors.forename: Sophie
authors.initials: S
authors.lastname: Mouillet-Richard
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000502:physiology; D018621:PrPC Proteins / Q000378:metabolism / Q000502:physiology*; D018620:PrPSc Proteins / Q000378:metabolism; D017096:Prion Diseases / Q000378:metabolism / Q000503:physiopathology*; D011328:Prions / Q000378:metabolism / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D010446:Peptide Fragments; D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions; D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; C082632:prion protein (106-126); D003300:Copper; D019255:NADPH Oxidases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C548267:ALPL protein, human; D000469:Alkaline Phosphatase; D051722:ADAM Proteins; D000072198:ADAM17 Protein; D002118:Calcium