Signaling via NF-κB in the nervous system

Nuclear factor kappa B (NF-κB) is an inducible transcription factor present in neurons and glia. Recent genetic models identified a role for NF-κB in neuroprotection against various neurotoxins. Furthermore, genetic evidence for a role in learning and memory is now emerging. This review highlights our current understanding of neuronal NF-κB in response to synaptic transmission and summarizes potential physiological functions of NF-κB in the nervous system. This article contains a listing of NF-κB activators and inhibitors in the nervous system, furthermore specific target genes are discussed. Synaptic NF-κB activated by glutamate and Ca2+ will be presented in the context of retrograde signaling. A controversial role of NF-κB in neurodegenerative diseases will be discussed. A model is proposed explaining this paradox as deregulated physiological NF-κB activity, where novel results are integrated, showing that p65 could be turned from an activator to a repressor of anti-apoptotic genes.