Cofactor involvement in prion propagation

Abstract

Pure amyloid proteins are responsible for the transmissible properties of yeast prions (Tanaka et al., Nature 428(6980):323-328, 2004; Tanaka et al., Cell 121(1):49-62, 2005; King and Diaz-Avalos, Nature 428(6980):319-323, 2004). However, it is currently unknown whether the infectious properties of mammalian prions can also be explained by a protein-only mechanism in which a host-encoded protein, PrP C, undergoes a conformational change into an infectious conformer, PrP Sc. Recent studies have shown that non-proteinaceous cofactors are necessary for the formation of PrP Sc and mammalian prion infectivity in vitro. Reconstitution studies suggest that different prion variants may preferentially propagate with specific classes of cofactor molecules. The pathogenic roles played by putative prion cofactors remain to be elucidated.