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.
Mattson
M P
MP
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA. mattsonm@grc.nia.nih.gov
Meffert
M K
MK
D002470:Cell Survival; D018450:Disease Progression; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction
D006133:Growth Substances; D016328:NF-kappa B