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• W1557182452 abstract "The accumulation of an abnormal, protease-resistant form of the protein PrP (PrP-res) in hosts with scrapie and related transmissible spongiform encephalopathies appears to be important in disease pathogenesis. To gain insight into the mechanism of PrP-res accumulation and the in vivo antiscrapie activity of certain polyanions, we have studied effects of sulfated glycans on PrP metabolism in scrapie-infected neuroblastoma cells. Pentosan polysulfate, like the amyloid-binding dye Congo red, potently inhibited the accumulation of PrP-res in these cells without apparent effects on the metabolism of the normal isoform. The inhibition was due primarily to prevention of new PrP-res accumulation rather than destabilization of preexisting PrP-res. PrP-res accumulation remained depressed in the cultures after removal of the inhibitors. The activities of other sulfated glycans, nonsulfated polyanions, dextran, and DEAE-dextran were compared with those of pentosan polysulfate and Congo red. This comparison provided evidence that the density of sulfation and molecular size are factors influencing anti-PrP-res activity of sulfated glycans. The relative potencies of these compounds corresponded well with their previously determined antiscrapie activities in vivo, suggesting that the prophylactic effects of sulfated polyanions may be due to inhibition of PrP-res accumulation. Since PrP-res amyloid is known to contain sulfated glycosaminoglycans, we reason that these inhibitors may competitively block an interaction between PrP and endogenous glycosaminoglycans that is essential for its accumulation in a protease-resistant, potentially amyloidogenic state." @default.
• W1557182452 created "2016-06-24" @default.
• W1557182452 creator A5018124229 @default.
• W1557182452 creator A5049683156 @default.
• W1557182452 date "1993-02-01" @default.
• W1557182452 modified "2023-10-14" @default.
• W1557182452 title "Sulfated polyanion inhibition of scrapie-associated PrP accumulation in cultured cells" @default.
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• W1557182452 doi "https://doi.org/10.1128/jvi.67.2.643-650.1993" @default.
• W1557182452 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/237415" @default.
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• W1557182452 hasPublicationYear "1993" @default.
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