NF-κB SIGNALING IN CEREBRAL ISCHEMIA

The transcription factor NF-kappa B is a key regulator of hundreds of genes involved in cell survival and inflammation. There is ample evidence that NF-kappa B is activated in cerebral ischemia, mainly in neurons. Despite its well known role as an antiapoptotic factor, in cerebral ischemia NF-kappa B contributes to neuronal cell death, at least if the ischemia is severe enough to lead to irreversible brain damage. In contrast, NF-kappa B also seems to be responsible for the preconditioning effect of a transient and sublethal ischemia, perhaps by dampening its own subsequent full activation. Among the five NF-kappa B subunits, RelA and p50 are responsible for the detrimental effect in cerebral ischemia. Activation of NF-kappa B signaling is mediated by the upstream kinase inhibitor of kappaB kinase and is triggered by hypoxia, reactive oxygen species, and several inflammatory mediators. Interestingly, the complex NF-kappa B signaling pathway provides drug targets at several levels. Modulation of NF-kappa B signaling has the potential to interrupt multiple inflammatory and apoptotic mechanisms through one specific molecular target. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.