NF-kappaB signaling in cerebral ischemia.

Abstract

The transcription factor NF-kappaB is a key regulator of hundreds of genes involved in cell survival and inflammation. There is ample evidence that NF-kappaB is activated in cerebral ischemia, mainly in neurons. Despite its well known role as an antiapoptotic factor, in cerebral ischemia NF-kappaB contributes to neuronal cell death, at least if the ischemia is severe enough to lead to irreversible brain damage. In contrast, NF-kappaB 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-kappaB subunits, RelA and p50 are responsible for the detrimental effect in cerebral ischemia. Activation of NF-kappaB 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-kappaB signaling pathway provides drug targets at several levels. Modulation of NF-kappaB signaling has the potential to interrupt multiple inflammatory and apoptotic mechanisms through one specific molecular target.

DOI: 10.1016/j.neuroscience.2008.07.007
0500200920102011201220132014201520162017
Citations per Year

3,021 Citations

Semantic Scholar estimates that this publication has 3,021 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Ridder2009NFkappaBSI, title={NF-kappaB signaling in cerebral ischemia.}, author={Dirk A. Ridder and Markus Schwaninger}, journal={Neuroscience}, year={2009}, volume={158 3}, pages={995-1006} }