Recent progress in prion and prion-like protein aggregation

Abstract

Prion diseases and prion-like protein misfolding diseases involve the accumulation of abnormally aggregated forms of the normal host proteins, such as prion protein and Tau protein. These proteins are special because of their self-duplicating and transmissible characteristics. Such abnormally aggregated proteins mainly formed in neurons, cause the neurons dysfunction, and finally lead to invariably fatal neurodegenerative diseases. Prion diseases appear not only in animals, such as bovine spongiform encephalopathy in cattle and scrapie in sheep, but also in humans, such as Creutzfeldt-Jacob disease, and even the same prion or prion-like proteins can have many different phenotypes. A lot of biological evidence has suggested that the molecular basis for different strains of prions could be hidden in protein conformations, and the misfolded proteins with conformations different from the normal proteins have been proved to be the main cause for protein aggregation. Crowded physiological environments can be imitated in vitro to study how the misfolding of these proteins leads to the diseases in vivo. In this review, we provide an overview of the existing structural information for prion and prion-like proteins, and discuss the post-translational modifications of prion proteins and the difference between prion and other infectious pathogens. We also discuss what makes a misfolded protein become an infectious agent, and show some examples of prion-like protein aggregation, such as Tau protein aggregation and superoxide dismutase 1 aggregation, as well as some cases of prion-like protein aggregation in crowded physiological environments.