NF-κB in the survival and plasticity of neurons

The transcription factor nuclear factor kappa-B (NF-κB) is involved in regulating responses of neurons to activation of several different signaling pathways in a variety of physiological and pathological settings. During development of the nervous system NF-κB is activated in growing neurons by neurotrophic factors and can induce the expression of genes involved in cell differentiation and survival. In the mature nervous system NF-κB is activated in synapses in response to excitatory synaptic transmission and may play a pivotal role in processes such as learning and memory. NF-κB is activated in neurons and glial cells in acute neurodegenerative conditions such as stroke and traumatic injury, as well as in chronic neurodegenerative conditions such as Alzheimer's disease. Activation of NF-κB in neurons can promote their survival by inducing the expression of genes encoding anti-apoptotic proteins such as Bcl-2 and the antioxidant enzyme Mn-superoxide dismutase. On the other hand, by inducing the production and release of inflammatory cytokines, reactive oxygen molecules and excitotoxins, activation of NF-κB in microglia and astrocytes may contribute to neuronal degeneration. Emerging findings suggest roles for NF-κB as a mediator of effects of behavioral and dietary factors on neuronal plasticity. NF-κB provides an attractive target for the development of novel therapeutic approaches for a range of neurological disorders.