NR ASZW
AU Kocisko,D.A.; Engel,A.L.; Harbuck,K.; Arnold,K.M.; Olsen,E.A.; Raymond,L.D.; Vilette,D.; Caughey,B.W.
TI Comparison of protease-resistant prion protein inhibitors in cell cultures infected with two strains of mouse and sheep scrapie
QU Neuroscience Letters 2005 Nov 11; 388(2): 106-11
PT journal article
AB The transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases. A primary therapeutic target for TSE intervention has been a protease-resistant form of prion protein known as PrPsc or PrPres. In vitro testing of mouse scrapie-infected cell cultures has identified many PrPres inhibitors that also have activity in vivo. Here we identify 32 new inhibitors of two strains of mouse scrapie PrPres. Furthermore, to investigate the species-specificity of these and other PrPres inhibitors, we have developed a high-throughput cell culture assay based on Rov9 cells chronically-infected with sheep scrapie. Of 32 inhibitors of murine PrPres that were also tested in the Rov9 cells, only six showed inhibitory activity against sheep PrPres. The three most potent inhibitors of both murine and ovine PrPres formation (with 50% inhibition at < or =5 microM) were tannic acid, pentosan polysulfate and Fe(III) deuteroporphyrin 2,4-bisethyleneglycol. The latter two have anti-mouse scrapie activity in vivo. These results identify new inhibitors of murine and ovine PrPres formation and reinforce the idea that compounds effective against PrPres from one species or strain cannot be assumed to be active against others.
MH Animals; Cell Line; Comparative Study; Deuteroporphyrins/pharmacology; Enzyme Inhibitors/pharmacology; Epithelial Cells/cytology; Ferric Compounds/pharmacology; Mice; Pentosan Sulfuric Polyester/pharmacology; PrPsc Proteins/*antagonists & inhibitors/metabolism; Rabbits; Research Support, U.S. Gov't, Non-P.H.S.; Scrapie/*drug therapy/*metabolism; Sheep; Species Specificity; Tannins/*pharmacology
AD Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. DKocisko@niaid.nih.gov
SP englisch
PO Irland