1. ¹Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD, USA
2. ²Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
3. ³Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Correspondence: MP Mattson, Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Tel: 410 558 8463; Fax: 410 558 8465; E-mail: mattsonm@grc.nia.nih.gov or mkm@jhmi.edu

Received 4 October 2005; Revised 2 November 2005; Accepted 3 November 2005; Published online 6 January 2006.

Abstract

Here we review evidence of roles for NF-B in the regulation of developmental and synaptic plasticity, and cell survival in physiological and pathological settings. Signaling pathways modulating NF-B activity include those engaged by neurotrophic factors, neurotransmitters, electrical activity, cytokines, and oxidative stress. Emerging findings support a pivotal role for NF-B as a mediator of transcription-dependent enduring changes in the structure and function of neuronal circuits. Distinct subunits of NF-B may uniquely affect cognition and behavior by regulating specific target genes. NF-B 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-B 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-B in neurons are being elucidated and may provide novel targets for therapeutic intervention in various neurological disorders.