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.Cell Death and Differentiation (2006) 13, 852-860. doi:10.1038/sj.cdd.4401837; published online 6 January 2006.[1]References
- Roles for NF-kappaB in nerve cell survival, plasticity, and disease. Mattson, M.P., Meffert, M.K. Cell Death Differ. (2006) [Pubmed]
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