Signaling via NF-kappaB in the nervous system.
Nuclear factor kappa B (NF-kappaB) is an inducible transcription factor present in neurons and glia. Recent genetic models identified a role for NF-kappaB 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-kappaB in response to synaptic transmission and summarizes potential physiological functions of NF-kappaB in the nervous system. This article contains a listing of NF-kappaB activators and inhibitors in the nervous system, furthermore specific target genes are discussed. Synaptic NF-kappaB activated by glutamate and Ca2+ will be presented in the context of retrograde signaling. A controversial role of NF-kappaB in neurodegenerative diseases will be discussed. A model is proposed explaining this paradox as deregulated physiological NF-kappaB activity, where novel results are integrated, showing that p65 could be turned from an activator to a repressor of anti-apoptotic genes.
Institut für Neurobiochemie Universität Witten/Herdecke, Stockumer Street 10, D-58448 Witten, Germany.
Barbara
B
Kaltschmidt
Darius
D
Widera
Christian
C
Kaltschmidt
D000818:Animals; D005786:Gene Expression Regulation; D007858:Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D008954:Models, Biological; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D009424:Nervous System Physiological Phenomena; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D016328:NF-kappa B