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

C. Julius^1,

M. Heikenwalder^1,

¹ Institute of Neuropathology, University Hospital of Zürich, Zürich, Switzerland
² Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, USA
³ Department of Neuropathology, University of Freiburg, Freiburg, Germany
⁴ Institute for Genetics, University of Cologne, Cologne, Germany

Correspondence
A. Aguzzi
adriano.aguzzi{at}usz.ch

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/IKKβ 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 IKKβ or IKK in nearly all neuroectodermal cells, including neurons, astrocytes and oligodendrocytes, and in mice containing a non-phosphorylatable IKK subunit (IKK^AA/AA). 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.

These authors contributed equally to this work.