title: Prion diseases and the 'protein only' hypothesis: a theoretical dynamic study.
abstract: In the 'protein only' hypothesis, prion diseases are thought to result from the conformational change of a normal isoform of a prion protein (PrPC) to a protease-resistant, pathogenic form called PrPSc. This conversion rests on an autocatalytic process requiring the presence of pre-existing PrPSc. Theoretical kinetic analysis of the dynamic process, including the turnover of the normal prion protein, shows that the system exhibits bistability properties, indicating that the very slow accumulation of the abnormal form of the protein in the brain could in fact be the consequence and not the cause of the disorders. The cause would be a transition between two alternative steady states of the system. The presence of a small amount of the PrPSc protein in lymphocytes does not necessarily constitute any indication of a non-symptomatic but infectious pathogenic state. Moreover, infectious prion particles should not be seen as necessarily composed of the abnormal isoform of the protein, as usually stated. Particles containing only an excess of the normal form of the protein might also be pathogenic. Compounds that can act on the turnover rate of the normal PrPC protein could be a therapeutic strategy against prion diseases.
authors: Service d'Imagerie Cellulaire, URA 1116, Université Paris-Sud, Centre d'Orsay, France.
authors: M
authors: M
authors: Laurent
mesh_terms: D000818:Animals; D002417:Cattle; D006801:Humans; D007700:Kinetics; D018621:PrPC Proteins / Q000737:chemistry / Q000378:metabolism*; D018620:PrPSc Proteins / Q000737:chemistry / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D018621:PrPC Proteins; D018620:PrPSc Proteins