| First Author | Herrmann O | Year | 2005 |
| Journal | Nat Med | Volume | 11 |
| Issue | 12 | Pages | 1322-9 |
| PubMed ID | 16286924 | Mgi Jnum | J:248942 |
| Mgi Id | MGI:6093766 | Doi | 10.1038/nm1323 |
| Citation | Herrmann O, et al. (2005) IKK mediates ischemia-induced neuronal death. Nat Med 11(12):1322-9 |
| abstractText | 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. |
