IKK mediates ischemia-induced neuronal death

@article{Herrmann2005IKKMI,
  title={IKK mediates ischemia-induced neuronal death},
  author={Oliver Herrmann and Bernd Baumann and Rossana de Lorenzi and Sajjad Muhammad and Wen Zhang and Jens Kleesiek and Maximillian V. Malfertheiner and Martin Köhrmann and Ioana Potrovita and Ira Maegele and Cordian Beyer and James R Burke and Mazahir T. Hasan and Hermann Prof. Dr. Bujard and Thomas Wirth and Manolis Pasparakis and Markus Schwaninger},
  journal={Nature Medicine},
  year={2005},
  volume={11},
  pages={1322-1329}
}
The IκB kinase complex IKK is a central component of the signaling cascade that controls NF-κB–dependent gene transcription. So far, its function in the brain is largely unknown. Here, we show that IKK is activated in a mouse model of stroke. To investigate the function of IKK in brain ischemia we generated mice that contain a targeted deletion of Ikbkb (which encodes IKK2) in mouse neurons and mice that express a dominant inhibitor of IKK in neurons. In both lines, inhibition of IKK activity… 
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257 Citations
Highly Influential Citations
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257 Citations

NF-κB signalling in cerebral ischaemia
TLDR
There is evidence that IKK/NF-kappaB signalling contributes to ischaemic brain damage and may provide suitable drug targets for the treatment of stroke.
Acute inhibition of TAK1 protects against neuronal death in cerebral ischemia
TLDR
This study demonstrates that TAK1 is a central target for short-term inhibition of key signaling pathways and neuroprotection in cerebral ischemia and upregulated another MAP3K, apoptosis signal-regulating kinase-1, which is able to compensate for TAK 1 inhibition.
NF-κB signaling in cerebral ischemia
Neuroprotective potential of the NF-κB inhibitor peptide IKK-NBD in cerebral ischemia-reperfusion injury
Astrocyte-specific IKK2 activation in mice is sufficient to induce neuroinflammation but does not increase susceptibility to MPTP
Deletion of Nuclear Factor kappa B p50 Subunit Decreases Inflammatory Response and Mildly Protects Neurons from Transient Forebrain Ischemia-induced Damage.
TLDR
NF-κB regulates the outcome of transient forebrain ischemia in middle-aged subjects in a sex-specific way, having an impact not only on neuronal death but also specific inflammatory responses and neurogenesis.
Bim and Noxa Are Candidates to Mediate the Deleterious Effect of the NF-κB Subunit RelA in Cerebral Ischemia
TLDR
The deleterious function in cerebral ischemia is specific for the NF-κB subunit RelA and may be mediated through Bim and Noxa, and expression of the proapoptotic BH3 (Bcl-2 homology domain 3)-only genes Bim-Noxa in cerebral waschemia depended onrelA and the upstream kinase IKK (IκB kinase).
p53-mediated neuronal cell death in ischemic brain injury
TLDR
In various stroke models, p53 deficiency or applications of p53 inhibitors can significantly attenuate brain damage and has become a therapeutic target against stroke pathology.
Oxidative Stress Increases Phosphorylation of IκB Kinase-α by Enhancing NF-κB-Inducing Kinase after Transient Focal Cerebral Ischemia
  • Y. Song, Min-Soo Kim, P. Chan
  • Biology, Chemistry
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2010
TLDR
The results suggest that augmentation of NIK, IKKα, and pH3 in response to oxidative stress is involved in cell death after cerebral ischemia (or stroke).
IKK2/NF-κB signaling protects neurons after traumatic brain injury
  • M. Mettang, S. Reichel, T. Wirth
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2018
TLDR
This study demonstrates that physiological neuronal IKK/NF‐κB signaling is necessary and sufficient to protect neurons from trauma consequences and identifies elevated levels of the proapoptotic mediators Bax and Bad and enhanced expression of stress response genes.
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