NR AWHR
AU Julius,C.; Heikenwalder,M.; Pasparakis,M.; Prinz,M.; Schwarz,P.; Aguzzi,A.
TI The role of brain specific NF-kB activation in prion disease
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions PA-29
PT Konferenz-Poster
AB
The Nuclear Factor-kB (NF-kB) pathway plays an essential role in immune responses involving induction of inflammation, proliferation and regulation of apoptosis. After scrapie-infection concomitant with first neuronal pathological changes NF-kB activity in the brain was shown to be enhanced in vivo. Furthermore the synthetic peptide PrP106-126 activates NF-kB in microglial cells in vitro. Microglia, involved in the immune response of the brain, most likely contribute in the process of neurodegeneration caused by prions. The IkB kinase (IKK) signalosome, consisting of the IKK-alpha and IKK-beta catalytic subunits and the IKK-gamma (also known as NEMO) regulatory subunit, is essential in the NF-kB pathway and necessary for NF-kB activation through pro-inflammatory signals. An ideal model to study the influence of NF-kB activation on prion disease would be a mouse that lacks IKK dependent signaling. Unfortunately, mice with a non functional IKK-beta or IKK-gamma subunit are not viable.
We investigate prion propagation after intracerebral inoculation (i.c.) in mouse models with a brain specific depletion of IKK-beta and IKK-gamma. This is achieved through the Cre-lox system under the control of the brain specific promoter nestin.
Keywords: prions, IKK signalosome, NF-kB.
AD C. Julius, M. Heikenwalder, P. Schwarz, A. Aguzzi: Institute of Neuropathology, University Hospital Zürich, Switzerland; M. Pasparakis: Institute for Genetics, University of Cologne, Germany; M. Prinz: Institute of Neuropathology, Georg-August-Universität, Göttingen, Germany. E-mail: adriano@pathol.unizh.ch
SP englisch
PO Italien