title: Decoding the function of the N-terminal tail of the cellular prion protein to inspire novel therapeutic avenues for neurodegenerative diseases.
abstract: The cellular prion protein (PrP(C)), a cell surface glycoprotein involved in prion disorders, has been shown to mediate the toxicity of several pathological aggregates, including its own misfolded state and some oligomeric assemblies of the amyloid β peptide, which are thought to be primarily responsible for the synaptic dysfunction characterizing Alzheimer's disease. Thus, elucidating the physiological function of PrP(C), and how it could be corrupted by the interaction with misfolded proteins, may provide important insights to understand the pathological processes of prion and Alzheimer's diseases, and possibly other neurodegenerative disorders. In this manuscript, we review the data supporting a role for PrP(C) at the intersection of different neurodegenerative diseases, discuss potential mechanisms by which this protein could mediate neurotoxic signals, and examine therapeutic approaches that may arise from the identification of PrP(C)-directed compounds.
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy.
authors.forename: Nunzio
authors.initials: N
authors.lastname: Iraci
authors.affiliation: Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Stincardini
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy.
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Barreca
authors.affiliation: Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy. Electronic address: emiliano.biasini@marionegri.it.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Biasini
mesh_terms: D000818:Animals; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D018621:PrPC Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017096:Prion Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D018621:PrPC Proteins
keywords: Alzheimer; Aβ oligomers; Neurodegeneration; PrP(C); Prion