title: Role of prion protein aggregation in neurotoxicity.
abstract: In several neurodegenerative diseases, such as Parkinson, Alzheimer's, Huntington, and prion diseases, the deposition of aggregated misfolded proteins is believed to be responsible for the neurotoxicity that characterizes these diseases. Prion protein (PrP), the protein responsible of prion diseases, has been deeply studied for the peculiar feature of its misfolded oligomers that are able to propagate within affected brains, inducing the conversion of the natively folded PrP into the pathological conformation. In this review, we summarize the available experimental evidence concerning the relationship between aggregation status of misfolded PrP and neuronal death in the course of prion diseases. In particular, we describe the main findings resulting from the use of different synthetic (mainly PrP106-126) and recombinant PrP-derived peptides, as far as mechanisms of aggregation and amyloid formation, and how these different spatial conformations can affect neuronal death. In particular, most data support the involvement of non-fibrillar oligomers rather than actual amyloid fibers as the determinant of neuronal death.
authors.affiliation: Section of Pharmacology, Department of Internal Medicine, University of Genova, Genova 16132, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corsaro
authors.affiliation: Section of Pharmacology, Department of Internal Medicine, University of Genova, Genova 16132, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Thellung
authors.affiliation: Section of Pharmacology, Department of Internal Medicine, University of Genova, Genova 16132, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Villa
authors.affiliation: Section of Pharmacology, Department of Internal Medicine, University of Genova, Genova 16132, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Nizzari
authors.affiliation: Section of Pharmacology, Department of Internal Medicine, University of Genova, Genova 16132, Italy.
authors.forename: Tullio
authors.identifier: 0000-0002-1819-3811
authors.initials: T
authors.lastname: Florio
mesh_terms: D000818:Animals; D006801:Humans; D020125:Mutation, Missense; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism* / Q000635:transmission; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D066263:Protein Aggregation, Pathological / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D021381:Protein Transport; D012987:Soil / Q000737:chemistry
chemical_list: D011328:Prions; D012987:Soil