The Role of Chaperones in Prion Infection

The Role of Chaperones in Prion Infection

Prions are infectious proteins that cause neurodegenerative diseases called transmissible spongiform encephalopathy which affect several species, including humans. Chaperones are molecules that bind to the nascent peptide chain and fold the polypeptide chain into its secondary or tertiary structure. Prions affect the protein folding machinery or molecular chaperones of the cell which might lead to the formation of aggregates. The goal of this literature review is to highlight several functions of chaperones in prion infection, to draw attention that prions could be misfolded molecular chaperones, and to indicate the therapeutic applications of chaperones in prion infection.

Chaperones may perform a variety of functions in prion infection. Chaperones like Hsp104 and Ssa (from Hsp70 family) may promote prion aggregation inSaccharomyces cerevisiae. The over expression of chaperones such as Hsp104, Ssa1, and Ydj1p, inhibits prion propagation. Ssb, chemical chaperones, and chaperones found in E. coli also prevent prion growth. Chaperones such as GroEL and Hsp104 can make normal cellular prions resistant to protease activity and prevent the proteolysis of prion proteins. However, some chaperones such as BiP can interact with misfolded or abnormal proteins and recruit these proteins for proteosomal degradation. By comparing the properties of molecular chaperones and prions, it can be inferred that prions could be misfolded chaperones. Since chaperones play a crucial role in prion propagation many chaperones can be used as targets for therapeutic applications.