title: Prionics or the kinetic basis of prion diseases.
abstract: A comparative kinetic analysis of mechanisms of prion diseases based on the "protein only" hypothesis is presented. The Prusiner mechanism of autocatalytic conversion of a host protein into a genetically identical, but conformationally different, prion state requires cooperativity in order to work, given realistic values of rate parameters. It then becomes phenomenologically indistinguishable from the Lansbury mechanism of plaque formation which is also a form of (passive) autocatalysis. Though the two kinds of mechanisms still may differ on the question which of the two monomeric protein conformations is the favoured equilibrium state they both require an aggregated state as the form that is eventually favored at equilibrium. While these considerations allow for a critical comparison of the mechanisms they do not yet tell us what the actual mechanism of infection is. Experiments rather indicate that the infectious unit in vivo may still differ from an in vitro form of aggregated prion proteins. Hence aggregation of the prionic form is most probably a necessary, but possibly not sufficient, prerequisite of infection. Be that as it may, the premise of a linkage between prion aggregation and infection offers a very sensitive method for diagnosing the disease at a very early stage, using fluorescence cross-correlation analysis. The possible analogies to Alzheimer's disease make such a prospect a "hot topic".
authors.affiliation: Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Eigen
mesh_terms: D000494:Allosteric Regulation / Q000502:physiology; D000495:Allosteric Site / Q000502:physiology; D000544:Alzheimer Disease / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D017096:Prion Diseases / Q000503:physiopathology*; D011328:Prions / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D011328:Prions