NR AJJB
AU Perez,M.; Wandosell,F.; Colaco,C.; Avila,J.
TI Sulphated glycosaminoglycans prevent the neurotoxicity of a human prion protein fragment
QU Biochemical Journal 1998 Oct 15; 335(2): 369-74
PT journal article
AB Although a number of features distinguish the disease isoform of the prion protein (PrPsc) from its normal cellular counterpart (PrPc) in the transmissible spongiform encephalopathies (TSEs), the neuropathogenesis of these diseases remains an enigma. The amyloid fibrils formed by fragments of human PrP have, however, been shown to be directly neurotoxic in vitro. We show here that sulphated polysaccharides (heparin, keratan and chondroitin) inhibit the neurotoxicity of these amyloid fibrils and this appears to be mediated via inhibition of the polymerization of the PrP peptide into fibrils. This provides a rationale for the therapeutic effects of sulphated polysaccharides and suggests a rapid in vitro functional screen for TSE therapeutics.
MH Chondroitin/metabolism/pharmacology; Glycosaminoglycans/metabolism/*pharmacology; Heparin/metabolism/pharmacology; Human; Keratan Sulfate/metabolism/pharmacology; Neuroblastoma/drug therapy/pathology; Peptide Fragments/chemical synthesis/metabolism; Prions/*metabolism/*toxicity/ultrastructure; Support, Non-U.S. Gov't
AD Centro de Biolog approximately ia Molecular, Universidad Autonoma de Madrid, 28049-Madrid, Spain.
SP englisch
PO England