NR AXIM
AU Bahlo,A.; Lindner,N.; Flechsig,E.; Klein,M.A.
TI Unaltered Neurodegeneration in Prion-infected Neurografts Devoid of BCL-2 or BAX
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.22
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Prion diseases or transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative disorders such, as Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle and scrapie in sheep. It has been postulated that the disease-associated prion protein (PrPsc) is the infectious agent, which replicates by conversion of the cellular prion protein (PrPc) into a likeness of itself. Accumulation of PrPsc and neuropathological changes, such as spongiosis, gliosis and neuronal death are typical hallmarks of prion diseases, but the mechanisms how prions proceed to damage neurons are still unknown. Prion-induced neuronal cell death appears to be associated with apoptosis. Expression levels of the apoptotic proteins like BAX and BCL-2 are altered in hippocampal neurons of prion-infected hamsters. Recently, an anti-apoptotic function against BAX-induced apoptosis has been postulated for PrPc in cultured cells and binding of PrPc to the carboxy-terminal region of BCL-2 has been shown in a yeast two-hybrid system. To further characterize the role of BAX and BCL-2 in prion-induced neurodegeneration, we transplanted either BAX- or BCL-2-deficient neuroectodermal tissue into the brain of PrP null recipient mice. After long-term exposure to mouse RML prions, typical histopathological features of the disease, such as gliosis, spongiosis and PrPsc accumulation were found strictly restricted to the grafted tissues. Moreover, apoptosis was detectable in the brain grafts by staining for activated caspase-3 and TUNEL. Our results indicate that BAX and BCL-2 are not directly involved in the mechanisms leading to the neurodegeneration in prion diseases.
AD A. Bahlo, N. Lindner, E. Flechsig, M.A. Klein, Institute for Virology, University of Wuerzburg, Germany
SP englisch
PO Schottland