1887

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

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2008-06-01
2019-11-16
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