HEPARIN-LIKE MOLECULES BIND DIFFERENTIALLY TO PRION-PROTEINS AND CHANGE THEIR INTRACELLULAR METABOLIC-FATE

PrP(Sc) is the only known component of the scrapie prion. The difference between PrP(Sc) and its normal isoform PrP(c) is probably conformational, since no difference has been found in the amino acid sequence or postranslational modifications between both proteins. Heparan sulfate (HS) has been shown to be a component of amyloid plaques in a number of diseases including the prion diseases. We now present evidence that PrP can specifically bind to heparin-like compounds and that this interaction might have a physiological significance. HS can increase the concentration of PrP in normal neuroblastoma cells, whereas low molecular weight heparin (LMWH) does not. In contrast, LMWH and other heparin-like molecules, excluding HS, can inhibit the synthesis of PrP(Sc) in scrapie infected cells and reverse their phenotype back to normal as judged by measurement of PrP(Sc) by immunoblotting and by infectivity experiments. Whether an interaction between PrP and glycosaminoglycans plays a direct role in the conversion of PrP(c) into PrP(Sc) remains to be established. (C) 1993 Wiley-Liss, Inc.