NR AXLS
AU Ertmer,A.; Gilch,S.; Schätzl,H.M.; Heiseke,A.
TI Induction of Cellular Autophagy Reduces Prions
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Oral Abstracts FC4.5
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Vortrag
AB The tyrosin kinase inhibitor imatinib can significantly reduce PrPsc and infectious prions in prion-infected cells, by increasing lysosomal clearance for prions (Ertmer et al., 2004). Imatinib treatment of prion-infected mice showed that this anti-prion effect is found also in vivo to a certain extent (Yun et al., 2007). Recently, we have reported that imatinib causes a general induction of cellular autophagy (Ertmer et al., 2007). Here, we provide experimental evidence that induction of autophagy is indeed responsible for reducing cellular levels of PrPsc. Application of inhibitors of autophagy in parallel with imatinib antagonised the anti-prion effect of imatinib. On the other hand, the mTOR inhibitor rapamycin which is an inducer of autophagy reduced PrPsc similar to imatinib. Of note, autophagy inhibitors alone increased PrPsc. Our studies also shed light on the reciprocal adapting of prions to cells and of cells to prions and which positive or negative role autophagy plays in this scenario. It is conceivable that a certain level of autophagy is beneficial for prion propagation, whereas too much results in total cellular clearance, eventually accompanied by apoptotic cell death. Overall, we demonstrate that inducers of autophagy have the potential to interfere with prion propagation in infected cells. Future studies have to show whether induction of autophagy can be used as a novel experimental avenue for therapy against prion diseases.
AD A. Ertmer, S. Gilch, H.M. Schätzl, A. Heiseke, Institute of Virology, Technical University of Munich, Germany
SP englisch
PO Schottland