Prion diseases: Dynamics of the infection and properties of the bistable transition

Prion diseases are thought to result from a pathogenic, conformational chan ge in a cellular protein, the prion protein. The pathogenic lsoform seems t o convert the normal isoform in an autocatalytic process. In contrast to th e conditions used for in vitro studies of enzyme kinetics, the concentratio n of the catalyst is not much lower than that of the substrate in the cours e of infection. This feature may endow the system with a time-hierarchy all owing the pathogenic isoform to relax very slowly in the course of Infectio n. This may contribute to the long incubation periods observed in prion dis eases. The dynamic process of prion propagation, including turnover of the cellular prion protein, displays bistable properties. Sporadic prion diseas es may result from a change in one of the parameters associated with metabo lism of the prion protein. The bistable transition observed in sporadic dis ease is reversible, whereas that observed in cases of exogenous contaminati on is irreversible. This model is consistent with the occurrence of rare, s poradic forms of prion diseases. It may also explain why only some individu als of a cohort develop a prion disease following transient food contaminat ion.