Abstract

The PrP propensity to adopt different structures is tightly linked to transmissible spongiform encephalopathies (TSE) which include Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scjeinker (GSS) and Kuru syndrome. In most cases, TSE is associated with the accumulation in the brain of an abnormally folded protease-resistant protein, PrPSc or PrPres, which is derived from a cellular host-encoded protease-sensitive conformer, designated PrPC. The prion propagation in the brain is postulated to occur via a conformational change of PrPC into the amyloidogenic form PrPSc, characterized by a high β sheet content. The characterization of PrPSC oligomers as well as their biological activity is currently an area of active research. Indeed, PrPSc 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 acheave a better understanding of the pathological events at the molecular level.

Keywords: transmissible spongiform encephalopathies, kinetic intermediate, oligomerization, soluble oligomers, protein misassembly, amyloid, catalyse, nucleus, seed