title: NF-κB and epigenetic mechanisms as integrative regulators of brain resilience to anoxic stress.
abstract: Brain cells display an amazing ability to respond to several different types of environmental stimuli and integrate this response physiologically. Some of these responses can outlive the original stimulus by days, weeks or even longer. Long-lasting changes in both physiological and pathological conditions occurring in response to external stimuli are almost always mediated by changes in gene expression. To effect these changes, cells have developed an impressive repertoire of signaling systems designed to modulate the activity of numerous transcription factors and epigenetic mechanisms affecting the chromatin structure. Since its initial characterization in the nervous system, NF-κB has shown to respond to multiple signals and elicit pleiotropic activities suggesting that it may play a pivotal role in integration of different types of information within the brain. Ample evidence demonstrates that NF-κB factors are engaged in and necessary for neuronal development and synaptic plasticity, but they also regulate brain response to environmental noxae. By focusing on the complexity of NF-κB transcriptional activity in neuronal cell death, it emerged that the composition of NF-κB active dimers finely tunes the neuronal vulnerability to brain ischemia. Even though we are only beginning to understand the contribution of distinct NF-κB family members to the regulation of gene transcription in the brain, an additional level of regulation of NF-κB activity has emerged as operated by the epigenetic mechanisms modulating histone acetylation. We will discuss NF-κB and epigenetic mechanisms as integrative regulators of brain resilience to anoxic stress and useful drug targets for restoration of brain function. This article is part of a Special Issue entitled: Brain Integration.
authors.affiliation: Department of Biomedical Sciences & Biotechnologies, University of Brescia and Istituto Nazionale di Neuroscienze, Italy.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Sarnico
authors.forename: Caterina
authors.initials: C
authors.lastname: Branca
authors.forename: Annamaria
authors.initials: A
authors.lastname: Lanzillotta
authors.forename: Vanessa
authors.initials: V
authors.lastname: Porrini
authors.forename: Marina
authors.initials: M
authors.lastname: Benarese
authors.forename: Pier Franco
authors.initials: PF
authors.lastname: Spano
authors.forename: Marina
authors.initials: M
authors.lastname: Pizzi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D002545:Brain Ischemia / Q000473:pathology*; D044127:Epigenesis, Genetic; D006801:Humans; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D016328:NF-kappa B