Glycosaminoglycan sulfation determines the biochemical properties of prion protein aggregates

Abstract

Prion diseases are transmissible neurodegenerative disorders associated with the conversion of the cellular prion protein, PrPC, to a misfolded isoform called PrPSc. Although PrPSc is a necessary component of the infectious prion, additional factors, or cofactors, have been shown to contribute to the efficient formation of transmissible PrPSc. Glycosaminoglycans (GAGs) are attractive cofactor candidates as they can be found associated with PrPSc deposits, have been shown to enhance PrP misfolding in vitro, are found in the same cellular compartments as PrPC and have been shown to be disease modifying in vivo. Here we investigated the effects of the sulfated GAGs, heparin and heparan sulfate ..