Prion protein oligomerization.

The PrP propensity to adopt different structures is tightly linked to transmissible spongiform encephalopathies (TSE) which include Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scjeinker (GSS) and Kuru syndrome. In most cases, TSE is associated with the accumulation in the brain of an abnormally folded protease-resistant protein, PrP Sc or PrPres, which is derived from a cellular host-encoded protease-sensitive conformer, designated PrP C. The prion propagation in the brain is postulated to occur via a conformational change of PrP C into the amyloidogenic form PrP Sc, characterized by a high beta sheet content. The characterization of PrP SC oligomers as well as their biological activity is currently an area of active research. Indeed, PrP Sc structural diversity was proposed several years ago as a hypothesis to explain the origin of "prion strain" diversity. As prion pathologies belong to protein miss-assembly diseases, investigation of PrP conformational dynamics and, more precisely, oligomerization pathways exploration will help to achieve a better understanding of the pathological events at the molecular level.