Role of prion protein oligomers in the pathogenesis of transmissible spongiform encephalopathies

Prion diseases, also known as transmissible spongiform -encephalopathies, are a group of neurodegenerative disorders associated with misfolding and aggregation of prion proteins. Although it is not completely known how structural changes in the prion protein induce neurodegeneration, it is widely accepted that formation of the misfolded prion protein (termed PrP^Sc) is both the triggering event in the -disease and the main component of the infectious agent responsible for disease transmission. A long-debated issue in prion diseases has been the exact composition and size of the PrP^Sc particle required for initiating brain degeneration and propagating disease. Old and recent evidence show that PrP^Sc is an oligomer composed of -several units of the prion protein monomer, folded into a β-sheet-rich conformation. In this article we discuss the potential roles of prion oligomers in both neurotoxicity and infectivity and the similarities of prion diseases to other neurodegenerative -diseases associated with protein misfolding and aggregation.