SULFATED GLYCOSAMINOGLYCANS PREVENT THE NEUROTOXICITY OF A HUMAN PRION PROTEIN-FRAGMENT

Although a number of features distinguish the disease isoform of the p rion protein (PrPSc) from its normal cellular counterpart (PrPc) in th e transmissible spongiform encephalopathies (TSEs), the neuropathogene sis of these diseases remains an enigma. The amyloid fibrils formed by fragments of human PrP have, however, been shown to be directly neuro toxic in vitro. We show here that sulphated polysaccharides (heparin, keratan and chondroitin) inhibit the neurotoxicity of these amyloid fi brils and this appears to be mediated via inhibition of the polymeriza tion of the PrP peptide into fibrils. This provides a rationale for th e therapeutic effects of sulphated polysaccharides and suggests a rapi d in vitro functional screen for TSE therapeutics.