NR AUTC
AU Yun,S.W.; Ertmer,A.; Flechsig,E.; Gilch,S.; Riederer,P.; Gerlach,M.; Schätzl,H.M.; Klein,M.A.
TI Imatinib mesylate delays prion neuroinvasion by inhibiting prion propagation in the periphery
QU TSE-Forum, 6. Kongress - Nationale TSE-Forschungsplattform, Greifswald 26.6.-28.6.2006, Poster: Therapie THE-08
PT Konferenz-Poster
AB We have shown in a previous study that a tyrosine kinase inhibitor, imatinib mesylate, induces clearance of disease-associated isoform of prion protein, PrPsc, via specific inhibition of c-Abl in prion-infected cell culture models (Ertmer et al., JBC, 2004). In this study, we assessed the in vivo effects of imatinib mesylate on prion disease using a scrapie-infected mouse model, and further investigated the prion infectivity of the drug-treated scrapie-infected N2a neuroblastoma cell line, ScN2a cells. We found that imatinib mesylate decreases the levels of PrPsc and prion infectivity significantly in scrapie-infected mouse spleens as well as in ScN2a cells. Moreover, the drug treatment at an early phase of peripheral scrapie infection delayed the appearance of PrPsc in the CNS and onset of clinical disease in mice. However, neither intraperitoneal nor intracerebral delivery of the drug exerted any PrPsc clearance effect in the CNS. Our results suggest that specific inhibition of the tyrosine kinase activity prevents prion from propagating in the periphery.
AD Seong-Wook Yun, Eckhard Flechsig, Michael A. Klein, Institute of Virology and Immunobiology; Seong-Wook Yun, Peter Riederer, Clinical Neurochemistry and NPF Center of Excellence, Clinic of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany; Alexa Ertmer, Sabine Gilch, Hermann M. Schätzl, Institute of Virology, Technical University of Munich, Munich, Germany; Manfred Gerlach, Clinic of Child and Adolescent Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany
SP englisch
PO Deutschland
EA Photo des in Greifswald gezeigten Posters, welches nach Auskunft von Prof. Schätzl aktueller als der Tagungsband ist, in dem der Titel mit der Erläuterung: "The tyrosine kinase inhibitor imatinib mesylate" beginnt, Details
OR Tagungsband