title: Signal transduction and epigenetic mechanisms in the control of microglia activation during neuroinflammation.
abstract: Activation of microglia is a common denominator and a pathophysiological hallmark of the central nervous system (CNS) disorders. Damage or CNS disorders can trigger inflammatory responses in resident microglia and initiate a systemic immune system response. Although a repertoire of inflammatory responses differs in those diseases, there is a spectrum of transcriptionally activated genes that encode various mediators such as growth factors, inflammatory cytokines, chemokines, matrix metalloproteinases, enzymes producing lipid mediators, toxic molocules, all of which contribute to neuroinflammation. The initiation, progression and termination of inflammation requires global activation of gene expression, postranscriptional regulation, epigenetic modifications, changes in chromatin structure and these processes are tightly regulated by specific signaling pathways. This review focuses on the function of "master regulators" and epigenetic mechanisms in microglia activation during neuroinflammation. We review studies showing impact of epigenetic enzyme inhibitors on microglia activation in vitro and in vivo, and critically discuss potential of such molecules to prevent/moderate pathological events mediated by microglia under brain pathologies. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger.
authors.affiliation: Laboratory of Molecular Neurobiology, Neurobiology Center, Nencki Institute of Experimental Biology, Warsaw, Poland. Electronic address: bozenakk@nencki.gov.pl.
authors.forename: Bozena
authors.initials: B
authors.lastname: Kaminska
authors.affiliation: Division of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia and Istituto Nazionale di Neuroscienze, Brescia, Italy.
authors.forename: Mariana
authors.initials: M
authors.lastname: Mota
authors.affiliation: Division of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia and Istituto Nazionale di Neuroscienze, Brescia, Italy; IRCCS, San Camillo Hospital, Venice, Italy. Electronic address: marina.pizzi@unibs.it.
authors.forename: Marina
authors.initials: M
authors.lastname: Pizzi
mesh_terms: D000818:Animals; D002493:Central Nervous System Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D044127:Epigenesis, Genetic; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000276:immunology; D015213:Neuroimmunomodulation; D015533:Transcriptional Activation
chemical_list: D016328:NF-kappa B
keywords: Epigenetics; HDAC inhibitors; Microglia; Neuroinflammation; Signaling pathways; Transcription regulation