Roles of nuclear factor κB in neuronal survival and plasticity

The transcription factor nuclear factor kappa B (NF-kappa B) is moving to the forefront of the fields of apoptosis and neuronal plasticity because of recent findings showing that activation of NF-kappa B prevents neuronal apoptosis 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 neurotrophic factors and in response to various cell stressors, Oxidative stress and elevation of intracellular Calcium levels are particularly important inducers of NF-kappa B activation, Activation of NF-kappa B can interrupt apoptotic biochemical cascades at relatively early steps, before mitochondrial dysfunction acid oxyradical production; Gene targets for NF-kappa B that may mediate its antiapoptotic actions include the antioxidant enzyme manganese superoxide dismutase, members of the inhibitor of apoptosis family of proteins, and the calcium-binding protein calbindin D28k. NF-kappa B is activated by synaptic activity and may play important roles in the process of learning and memory. The available data identify NF-kappa B as an important regulator of evolutionarily conserved biochemical and molecular cascades designed to prevent cell death and promote neuronal plasticity. Because NF-kappa B may play roles in a range of neurological disorders that involve neuronal degeneration and/or perturbed synaptic function, pharmacological and genetic manipulations of NF-kappa B signaling are being developed that may prove valuable in treating disorders ranging from Alzheimer's disease to schizophrenia.