NR ATIM
AU Geissen,M.; Groschup,M.H.
TI Identification of PrPres inhibitors using cell culture based high throughput screening of substance libraries
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Cell Biology of PrPc and PrPsc CELL-44
PT Konferenz-Poster
AB
Transmissible Spongiform Encephalopathies are infectious neurodegenerative diseases including Creutzfeldt-Jakob Disease (CJD), variant CJD, Kuru, Bovine Spongiform Encephalopathy (BSE) and Scrapie. Prion diseases are characterised by spongiform degeneration of the central nervous system caused by the aggregation and accumulation of a Proteinase K resistant variant of the cellular prion protein. Cell death and degeneration of neuronal tissue finally occurs.
The aim of the study was to establish a screening system, that is suitable for cell culture application and allows the rapid and sensitive analysis of chemical compounds with regard to their inhibitory effect on PrPres accumulation in different scrapie infected cell lines. In a first step different cell lines were adapted to the 96-well plate format and analysed, using common inhibitors of PrPres accumulation. In this approach it was possible to identify three cell lines with different sensitivity to various inhibitors of PrPres. Using the most sensitive cell line, 10.000 compounds of a substance library (DIVERSet (ChemBridge) were screened to identify inhibitors and common structural features within these inhibitory substances. Rescreening in more resistant cell lines will identify chemical compounds, that might be capable for bioassays in mice.
AD M.Geissen, M.H.Groschup, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Germany
SP englisch
PO Deutschland