Abstract
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-κB (NF-κB) activity in the brain parallels the first pathological changes. The NF-κB pathway is essential for proliferation, regulation of apoptosis and immune responses involving induction of inflammation. The IκB kinase (IKK) signalosome is crucial for NF-κB signalling, consisting of the catalytic IKKα/IKKβ subunits and the regulatory IKKγ subunit. This study investigated the impact of NF-κB signalling on prion disease in mouse models with a central nervous system (CNS)-restricted elimination of IKKβ or IKKγ in nearly all neuroectodermal cells, including neurons, astrocytes and oligodendrocytes, and in mice containing a non-phosphorylatable IKKα subunit (IKKαAA/AA). In contrast to previously published data, the observed results showed no evidence supporting the hypothesis that impaired NF-κB signalling in the CNS impacts on prion pathogenesis.