NR AXTY
AU Nicolas,O.; Gavin,R.; Braun, N.; Urena,J.; Fontana,X.; Soriano,E.; Aguzzi,A.; Del Rio,J.A.
TI Bcl-2 Overexpression Rescues Cerebellar Degeneration in Prion-Deficient Mice that Overexpress Amino-Terminally Truncated Prion
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.76
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Prnp knockout mice that overexpress an amino-truncated form of PrPc (dPrP) are ataxic and display cerebellar cell loss and premature death. Studies on the molecular and intracellular events that trigger cell death in these mutants may contribute to elucidate the functions of PrPc and to the design of treatments for prion disease. Here we examined the effects of Bcl-2 overexpression in neurons on the development of the neurological syndrome and cerebellar pathology of dPrP. We show that dPrP overexpression activates the stress-associated kinases ERK1-2 in reactive astroglia, p38 and the phosphorylation of p53, which leads to the death of cerebellar neurons in mutant mice. We found that the expression of dPrP in cell lines expressing very low levels of PrPc strongly induces the activation of apoptotic pathways, thereby leading to caspase-3 activation and cell death, which can be prevented by coexpressing Bcl-2. Finally, we corroborate in vivo that neuronal-directed Bcl-2 overexpression in dPrP mice (dPrP Bcl-2) markedly reduces caspase-3 activation, glial activation, and neuronal cell death in cerebellum by improving locomotor deficits and life expectancy.
AD N. Oriol, G. Rosalina, M.U. Jesús, F. Xavier, S. Eduardo, J.A. Del Río, Institute for Research in Biomedicine of Barcelona, University of Barcelona, Department of Cell Biology, Spain; B. Nathalie, A. Adriano, University Hospital of Zürich, Institute of Neuropathology, Switzerland
SP englisch
PO Schottland
EA pdf-Datei und Poster (Postertitel: BCL-2 overexpression delays caspase-3 activation and rescues cerebellar degeneration in prion-deficient mice that overexpresses amino-terminally truncated prion)