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J Physiol Paris 92(3–4):289–292 Zanini S, Moschella V, Stefani A, Peppe A, Pierantozzi M, Galati S, Costa A, Mazzone P, Stanzione P (2009) Grammar improvement following deep brain stimulation of the subthalamic and the pedunculopontine nuclei in advanced Parkinson’s disease: a pilot study. Parkinsonism Relat Disord 15(8):606–609 NF-κB in Brain Diseases Cheng-Xin Gong Abstract Nuclear factor κB(NF-κB) is a family of major transcription factors that play various important roles under physiological and pathological conditions. NF-κB transcription factors are ubiquitously expressed, including neurons and glial cells of the central nervous system (CNS). The roles of NF-κB family in the CNS, both as mediators of transcriptional response to synaptic activity and in behavioral paradigms of learning and memory, are the focus of recent studies. In this chap- ter, the general structure, major functions, and the regulation of NF-κB signaling are first described concisely. Advances made in understanding of the roles of NF- κB in the CNS and in brain diseases are then reviewed in more detail. The NF-κB signaling pathway as a potential therapeutic target of brain diseases is discussed at the end. Keywords Alzheimer disease · Brain · Cytokines · Glial cells · Huntington’s disease · Iκ · IκB kinase · Ischemic and traumatic brain injury · Learning · Memory · Multiple sclerosis · Neuronal Plasticity · Neuroprotection · NF-κB · Nuclear factor · Parkinson’s disease · Rel family · Seizures · Synaptic transmis- sion · Therapeutic target · Transcription factor Abbreviations AD Alzheimer disease CNS Central nervous system HD Huntington’s disease IκB Inhibitor of NF-κB IKK IκB kinase IL Interleukin LTP Long-term potentiation NES Nuclear export signal C X. Gong (B) Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314-6399, USA e-mail: cxgong@mail.csi.cuny.edu 293 J.P. Blass (ed.), Neurochemical Mechanisms in Disease, Advances in Neurobiology 1, DOI 10.1007/978-1-4419-7104-3_10, C Springer Science+Business Media, LLC 2011 294 C X. Gong NF-κB Nuclear factor κB NIK NF-κB–inducing kinase NGF Nerve growth factor PD Parkinson’s disease SOD Superoxide dismutase SRD Signal response domain TNF Tumor necrosis factor Contents 1 Introduction 294 2 Structure of NF-κBandIκBFamily 295 3 General Biological Role of NF-κB 297 4 Regulation of NF-κB Signaling 299 5RoleofNF-κB Signaling in the CNS 301 5.1 NF-κBintheCNS 301 5.2 Activators and Inhibitors of NF-κBintheCNS 301 5.3 NF-κB–Regulating Genes in the CNS 302 5.4 Role of NF-κB in Synaptic Transmission and Neuronal Plasticity 302 5.5 Role of NF-κB in Learning and Memory 303 5.6 Role of NF-κB in Neuroprotection 303 5.7 Role of NF-κB in Glial Cells 304 6RoleofNF-κB in Brain Diseases 305 6.1 Role of NF-κB in Ischemic and Traumatic Brain Injury 305 6.2 Role of NF-κB in Seizures 306 6.3 Role of NF-κB in Alzheimer Disease (AD) 306 6.4 Role of NF-κB in Parkinson’s Disease (PD) and Huntington’s Disease (HD) . 307 6.5 Role of NF-κB in Multiple Sclerosis 308 7NF-κB Signaling Pathway as a Potential Therapeutic Target 309 References 310 1 Introduction Nuclear factor κB(NF-κB) is the prototype of a family of major transcription fac- tors that play an essential role in several aspects of physiological and pathological conditions. More than two decades ago, Sen and Baltimore (1986) discovered it as a nuclear factor that, when activated by agents such as bacterial lipopolysaccharide, binds to a 10-bp sequence in the enhancer region of the gene encoding the κ light chain of antibody molecules in B cells (hence, κB). Because of the growing biomed- ical importance of nuclear factors, studies on NF-κB and its implications have been a major area of research in the recent years. . delayed response is impaired in early Parkinson’s disease. Neuropsychology 11:171–179 Prasher D, Findley L (1991) Dopaminergic induced changes in cognitive and motor processing in Parkinson’s disease: an electrophysiological. Electroencephalogr Clin Neurophysiol 106:156–164 Hanninen T, Koivisto K, Reinikainen KJ, Helkala EL, Soininen H, Mykkänen L, Laakso M, Riekkinen PJ (1996) Prevalence of ageing-associated cognitive decline in an. following deep brain stimulation of the subthalamic and the pedunculopontine nuclei in advanced Parkinson’s disease: a pilot study. Parkinsonism Relat Disord 15(8):606–609 NF-κB in Brain Diseases Cheng-Xin