Roles for NF-kappaB in Nerve Cell Survival, Plasticity, and Disease

Here we review evidence of roles for NF-kappaB in the regulation of developmental and synaptic plasticity, and cell survival in physiological and pathological settings. Signaling pathways modulating NF-kappaB activity include those engaged by neurotrophic factors, neurotransmitters, electrical activity, cytokines, and oxidative stress. Emerging findings support a pivotal role for NF-kappaB as a mediator of transcription-dependent enduring changes in the structure and function of neuronal circuits. Distinct subunits of NF-kappaB may uniquely affect cognition and behavior by regulating specific target genes. NF-kappaB activation can prevent the death of neurons by inducing the production of antiapoptotic proteins such as Bcl-2, IAPs and manganese superoxide dismutase (Mn-SOD). Recent findings indicate that NF-kappaB plays important roles in disorders such as epilepsy, stroke, Alzheimer's and Parkinson's diseases, as well as oncogenesis. Molecular pathways upstream and downstream of NF-kappaB in neurons are being elucidated and may provide novel targets for therapeutic intervention in various neurological disorders.