Sequential Generation of Two Structurally Distinct Ovine Prion Protein Soluble Oligomers Displaying Different Biochemical Reactivities Original Research Article

In pathologies due to protein misassembly, low oligomeric states of the misfolded proteins rather than large aggregates play an important biological role. In prion diseases the lethal evolution is associated with formation of PrPSc, a misfolded and amyloid form of the normal cellular prion protein PrP. Although several molecular mechanisms were proposed to account for the propagation of the infectious agent, the events responsible for cell death are still unclear. The correlation between PrPC expression level and the rate of disease evolution on one side, and the fact that PrPSc deposition in brain did not strictly correlate with the apparition of clinical symptoms on the other side, suggested a potential role for diffusible oligomers in neuronal death.