NR AXXO
AU Tayebi,M.; David,M.; Hawke,S.
TI Epitope-Specific Anti-Prion Antibody-Mediated Neuronal Apoptosis in Neuronal Cell Line Cultures
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.80
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Molecular mechanisms underlying prion infection and the resulting replication/accumulation and neuronal death remain unknown. However, cellular prion protein, PrPc, seems to play an important role in these processes as PrPsc is not capable to initiate the neurotoxic effects associated with prion diseases if the former is lacking, indicating that it is directly involved in neurodegeneration.
Furthermore, cross-linking PrPc with specific anti-prion antibodies leads to neuronal apoptosis in vivo and to PrPc -dependent Fyn activation as well as modulation of calcium-dependent protein kinase C, suggesting a role in signal transduction.
We have used epitope-specific anti-prion antibodies on a well characterised cell culture model that possesses neuronal features and on rat dorsal root ganglia neurones in order to assess antibody-mediated apoptosis in vitro.
Here, we show that treatment of neuronal cells with anti-prion antibodies led to a dramatic over-expression of apolipoprotein E (apoE), release of cytochrome c from mitochondrial compartment into the cytosol and ultrastructural changes consistent with apoptosis. Our current data demonstrate that fine selection of antibodies to be used in prion therapeutic context is possible and even be encouraged although caution should be exerted when considering prion-mediated immunotherapy approaches.
AD M. Tayebi, The Royal Veterinary College, PID, UK; M. David, S. Hawke, University of Sydney, Medicine, Australia
SP englisch
PO Schottland