Conformational conversion of prion protein in prion diseases

Abstract

Prion diseases are a group of infectious fatal neurodegenerative diseases. The conformational conversion of a cellular prion protein (PrP(C)) into an abnormal misfolded isoform (PrP(Sc)) is the key event in prion diseases pathology. Under normal conditions, the high-energy barrier separates PrP(C) from PrP(Sc) isoform. However, pathogenic mutations, modifications as well as some cofactors, such as glycosaminoglycans, nucleic acids, and lipids, could modulate the conformational conversion process. Understanding the mechanism of conformational conversion of prion protein is essential for the biomedical research and the treatment of prion diseases. Particularly, the characterization of cofactors interacting with prion protein might provide new diagnostic and therapeutic strategies.