NR ATQL
AU Weber,P.; Piening,N.; Thomzig,A.; Beekes,M.; Kretzschmar,H.A.; Giese,A.
TI In vitro generated misfolded prion protein is infectious
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Structure of PrP and molecular determinants of infectivity STRCT-01
PT Konferenz-Poster
AB Prions are the causative infectious agents of transmissible spongiform encephalopathies and, thought to arise from misfolding and aggregation of prion protein (PrP). The structural conversion of cellular prion protein (PrPc) to the disease-associated misfolded isoform (PrPsc) can be modelled in vitro by protein misfolding cyclic amplification (PMCA). Wild-type hamsters challenged with proteinase resistant PrP (PrPres) generated in vitro by serial transmission PMCA showed accumulation of PrPsc in their brains and developed a neurological disease symptomatically indistinguishable from 263K hamster scrapie. PrPres generated by PMCA was associated with approximately ten times less infectivity than an equivalent quantity of brain-derived PrPsc. In contrast, animals challenged with PMCA-derived PrPres coupled to nitrocellulose (NC) particles exhibited cerebral PrPsc deposition and scrapie symptoms as fast as animals inoculated with NC particles incubated in infectious scrapie brain homogenate. These findings demonstrate for the first time, that - a specific delivery on carrier particles provided - in vitro generated misfolded prion protein is as infectious as brain derived PrPsc.
IN Die Autoren banden durch PMCA in vitro generiertes PrPres an Nitrozellulose und erzielten damit nach eigenen Angaben im Bioassay Infektiositäten, die denen von an Nitrozellulose gebundenem PrPsc aus Hirnhomogenaten entsprachen.
AD P.Weber, N.Piening, H.Kretzschmar, A.Giese, Ludwig-Maximilians-University, Center for neuropathology and prion diseases, Munich; A.Thomzig, M.Beekes, Robert-Koch-Institute, P24- Transmissible spongiform encephalopathies, Berlin
SP englisch
PO Deutschland