NR AOOI
AU Kocisko,D.A.; Baron,G.S.; Rubenstein,R.; Chen,J.; Kuizon,S.; Caughey,B.W.
TI New inhibitors of scrapie-associated prion protein formation in a library of 2000 drugs and natural products
QU Journal of Virology 2003 Oct; 77(19): 10288-94
PT journal article
AB
Transmissible spongiform encephalopathies (TSEs) are fatal, untreatable neurodegenerative diseases associated with the accumulation of a disease-specific form of prion protein (PrP) in the brain. One approach to TSE therapeutics is the inhibition of PrP accumulation. Indeed, many inhibitors of the accumulation of PrP associated with scrapie (PrPsc) in scrapie-infected mouse neuroblastoma cells (ScN(2)a) also have antiscrapie activity in rodents. To expedite the search for potential TSE therapeutic agents, we have developed a high-throughput screening assay for PrPsc inhibitors using ScN(2)a cells in a 96-well format. A library of 2000 drugs and natural products was screened in ScN(2)a cells infected with scrapie strain RML (Chandler) or 22L. Forty compounds were found to have concentrations causing 50% inhibition (IC(50)s) of PrPsc accumulation of MH
Animal; Antimalarials/pharmacology; Biological Factors/*pharmacology; Histamine Antagonists/pharmacology; Human; Phenols/pharmacology; Polymers/pharmacology; PrPsc Proteins/*antagonists & inhibitors AD
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA SP
englisch PO
USA