In acute stroke, neuronal apoptosis and inflammation are considered to be important mechanisms on the road to tissue loss and neurological deficit. Both apoptosis and inflammation depend on gene transcription. We have identified a signalling pathway that regulates transcription of genes involved in apoptosis and inflammation. In a mouse model of focal cerebral ischaemia, there is an induction of the cytokine TWEAK (tumour necrosis factor-like weak inducer of apoptosis) and its membrane receptor Fn14. TWEAK promotes neuronal cell death and activates the transcription factor NF-κB (nuclear factor κB) through the upstream kinase IKK [IκB (inhibitory κB) kinase]. In vivo, IKK is activated in neurons. Neuron-specific deletion of the subunit IKK2 or inhibition of IKK activity reduced the infarct size and neuronal cell loss. A pharmacological inhibitor of IKK also showed neuroprotective properties. IKK-dependent ischaemic brain damage is likely to be mediated by NF-κB, because neuron-specific inhibition of NF-κB through transgenic expression of the NF-κB superrepressor was found to reduce the infarct size. In summary, there is evidence that IKK/NF-κB signalling contributes to ischaemic brain damage and may provide suitable drug targets for the treatment of stroke.
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December 2006
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Conference Article|
October 25 2006
NF-κB signalling in cerebral ischaemia
M. Schwaninger;
M. Schwaninger
1
1Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
1To whom correspondence should be addressed (email markus.schwaninger@med.uni-heidelberg.de).
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I. Inta;
I. Inta
1Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
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O. Herrmann
O. Herrmann
1Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
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Publisher: Portland Press Ltd
Received:
June 26 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2006 The Biochemical Society
2006
Biochem Soc Trans (2006) 34 (6): 1291–1294.
Article history
Received:
June 26 2006
Citation
M. Schwaninger, I. Inta, O. Herrmann; NF-κB signalling in cerebral ischaemia. Biochem Soc Trans 1 December 2006; 34 (6): 1291–1294. doi: https://doi.org/10.1042/BST0341291
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