Roles of nuclear factor kappa B in neuronal survival and plasticity

The transcription factor nuclear factor kappa B (NF-kappa B) is moving to t he forefront of the fields of apoptosis and neuronal plasticity because of recent findings showing that activation of NF-kappa B prevents neuronal apo ptosis in various cell culture and in vivo models and because NF-kappa B is activated in association with synaptic plasticity. Activation of NF-kappa B was first shown to mediate antiapoptotic actions of tumor necrosis factor in cultured neurons and was subsequently shown to prevent death of various nonneuronal cells. NF-kappa B is activated by several cytokines and neurot rophic factors and in response to various cell stressors, Oxidative stress and elevation of intracellular Calcium levels are particularly important in ducers of NF-kappa B activation, Activation of NF-kappa B can interrupt apo ptotic biochemical cascades at relatively early steps, before mitochondrial dysfunction acid oxyradical production; Gene targets for NF-kappa B that m ay mediate its antiapoptotic actions include the antioxidant enzyme mangane se superoxide dismutase, members of the inhibitor of apoptosis family of pr oteins, and the calcium-binding protein calbindin D28k. NF-kappa B is activ ated by synaptic activity and may play important roles in the process of le arning and memory. The available data identify NF-kappa B as an important r egulator of evolutionarily conserved biochemical and molecular cascades des igned to prevent cell death and promote neuronal plasticity. Because NF-kap pa B may play roles in a range of neurological disorders that involve neuro nal degeneration and/or perturbed synaptic function, pharmacological and ge netic manipulations of NF-kappa B signaling are being developed that may pr ove valuable in treating disorders ranging from Alzheimer's disease to schi zophrenia.