Prion propagation in mice lacking central nervous system NF-κB signalling

Prions induce highly typical histopathological changes including cell death, spongiosis and activation of glia, yet the molecular pathways leading to neurodegeneration remain elusive. Following prion infection, enhanced nuclear factor- κ B (NF- κ B) activity in the brain parallels the first pathological changes. The NF- κ B pathway is essential for proliferation, regulation of apoptosis and immune responses involving induction of inflammation. The I κ B kinase (IKK) signalosome is crucial for NF- κ B signalling, consisting of the catalytic IKK α /IKK β subunits and the regulatory IKK γ subunit. This study investigated the impact of NF- κ B signalling on prion disease in mouse models with a central nervous system (CNS)-restricted elimination of IKK β or IKK γ in nearly all neuroectodermal cells, including neurons, astrocytes and oligodendrocytes, and in mice containing a non-phosphorylatable IKK α subunit ( IKKα AA/AA ). In contrast to previously published data, the observed results showed no evidence supporting the hypothesis that impaired NF- κ B signalling in the CNS impacts on prion pathogenesis.