Prion protein: structural features and related toxicity

Abstract

Transmissible spongiform encephalopathies, or prion diseases, is a group of infectious neurodegenerative disorders. The conformational conversion from cellular form (PrP(C)) to disease-causing isoform (PrP(Sc)) is considered to be the most important and remarkable event in these diseases, while accumulation of PrP(Sc) is thought to be the main reason for cell death, inflammation and spongiform degeneration observed in infected individuals. Although these rare but unique neurodegenerative disorders have attracted much attention, there are still many questions that remain to be answered. Knowledge of the scrapie agent structures and the toxic species may have significance for understanding the causes of the diseases, and could be helpful for rational design of novel therapeutic and diagnostic methods. In this review, we summarized the available experimental evidence concerning the relationship among the structural features, aggregation status of misfolded PrP and related neurotoxicity in the course of prion diseases development. In particular, most data supports the idea that the smaller oligomeric PrP(Sc) aggregates, rather than the mature amyloid fibers, exhibit the highest toxicity to the host.