title: Prions: a model of conformational disease?
abstract: The discovery that a protein could mimic viral and bacterial pathogens around 1980 by Stanley Prusiner was unexpected. Evidence shows now that Creutzfeldt-Jakob disease and related disorders are caused by prions. Prions and, for example neurodegeneratives diseases, arise from the same general disease mechanism. In each, there is abnormal unfolding and then aggregation of proteins. The protein conformational changes associated with the pathogenesis of protein misfolding disorders produce β sheet rich oligomers that are partially resistant to proteolysis and have a high tendency to form amyloid-like aggregates. It is important to distinguish between prions and amyloids: prions need not to polymerize into amyloid fibrils and can undergo self-propagation as oligomers. The prion diseases are characterized by the conformational conversion of PrP(c) to PrP(sc), the fundamental even underlying prion diseases. Despite the obvious differences between prions and conventional infectious microorganisms, prions fulfill the Koch's postulates. Meaningful treatments are likely to require cocktails of drugs that interfere with the conversion of precursor into prions and enhance the clearance of prions; such an approach may find application in the more common degenerative diseases.
authors.affiliation: Pôle Biologie-Pathologie-Physiologie, Université Paris Diderot-Paris Sorbonne Cité, Groupe Hospitalier Saint-Louis-Lariboisière - Fernand-Widal, Assistance publique-Hôpitaux de Paris, 1, avenue Claude-Vellefaux, 75010 Paris, France. Electronic address: frederic.morinet@sls.aphp.fr.
authors.forename: F
authors.initials: F
authors.lastname: Morinet
mesh_terms: D000682:Amyloid / Q000737:chemistry; D000818:Animals; D006801:Humans; D018621:PrPC Proteins / Q000737:chemistry; D018620:PrPSc Proteins / Q000737:chemistry; D017096:Prion Diseases / Q000453:epidemiology / Q000378:metabolism / Q000635:transmission / Q000662:veterinary; D011328:Prions / Q000737:chemistry*; D066263:Protein Aggregation, Pathological / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D057165:Proteostasis Deficiencies / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000682:Amyloid; D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions
keywords: Conformational disease; Degenerative disease; Feuillet β; Folding; Maladies conformationnelles; Maladies neurodégénératives; Prions; Repliement; β sheet