Prion protein aggregation

Abstract

Prion protein-mediated disorders appear to originate from the aggregation reactions of the prion protein. Like other amyloidogenic proteins, prion proteins form a range of fibrillar morphologies. The prefibrillar forms seen at the beginning of the reaction are also heterogeneous; hence it appears that structural heterogeneity sets in early during the aggregation reaction. The prion protein aggregation may therefore proceed from many different precursor states, and structural heterogeneity in prion fibrils might originate from the utilization of distinct nucleation and elongation mechanisms. This review discusses the current understanding of the structural heterogeneity inherent in the aggregation reactions of prion proteins. It examines how an understanding of the structural and provide molecular-level insights into the characteristic features of prion disorders, namely the infectious nature of the prion protein, prion strain phenomena and species barriers.