We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
IKK mediates ischemia-induced neuronal death.
- Authors
Herrmann, Oliver; Baumann, Bernd; de Lorenzi, Rossana; Muhammad, Sajjad; Zhang, Wen; Kleesiek, Jens; Malfertheiner, Max; Köhrmann, Martin; Potrovita, Ioana; Maegele, Ira; Beyer, Cordian; Burke, James R; Hasan, Mazahir T; Bujard, Hermann; Wirth, Thomas; Pasparakis, Manolis; Schwaninger, Markus
- Abstract
The IkappaB kinase complex IKK is a central component of the signaling cascade that controls NF-kappaB-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 markedly reduced infarct size. In contrast, constitutive activation of IKK2 enlarged the infarct size. A selective small-molecule inhibitor of IKK mimicked the effect of genetic IKK inhibition in neurons, reducing the infarct volume and cell death in a therapeutic time window of 4.5 h. These data indicate a key function of IKK in ischemic brain damage and suggest a potential role for IKK inhibitors in stroke therapy.
- Publication
Nature medicine, 2005, Vol 11, Issue 12, p1322
- ISSN
1078-8956
- Publication type
Journal Article
- DOI
10.1038/nm1323