NR AOSE
AU Ertmer,A.; Gilch,S.; Schätzl,H.M.
TI An inhibitor of a signalling cascade can cure prion-infected cells
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - IV-06
PT Konferenz-Poster
AB Up to now the pysiological role of PrPc and how PrPsc mediates cell death is rather unknown. Recent work pointed to a possible role for PrPc in signal transduction. In line with this, we reported the interaction of PrPc with several proteins involved in signal transduction pathways. In this context, we screened well-characterised substances interfering in signalling pathways in persistently prion-infected cells for their effects on PrPsc propagation. Here we describe one of these compounds, which showed to be strongly effective in PrPsc biogenesis. Upon treatment with this compound prion-infected cells could be rapidly cured in a time- and dose-dependent manner with no effect on biogenesis and cellular trafficking of PrPc. Whereas other anti-prion compounds usually inhibit the de-novo synthesis of PrPsc, this compound seems to directly affect pre-existing PrPsc by reducing its half-life time, resulting in the observed strong anti-prion effects. Although results in prion-infected animals are not yet available, the pharmacological features of this substance are promising. The drug is soluble in water, can be applied orally, crosses the blood-brain-barrier to a certain extend and shows rather low side effects. These features and the direct therapeutic effect on PrPsc make this compound an interesting drug for therapeutic in vivo studies. In these studies it could be elucidated whether signal transduction proteins can interfere in prion diseases and therefore provide novel targets prophylaxis and therapy of prion diseases.
AD A. Ertmer, S. Gilch, H.M. Schätzl, Prion Research Group, Institute of Virology, Technical University of Munich, Germany
SP englisch
PO Deutschland