title: Epigenetic changes in patients with multiple sclerosis.
abstract: Epigenetic changes influence gene expression without altering the DNA sequence. DNA methylation, histone modification and microRNA-associated post-transcriptional gene silencing are three key epigenetic mechanisms. Multiple sclerosis (MS) is a disease of the CNS with both inflammatory and neurodegenerative features. Although studies on epigenetic changes in MS only began in the past decade, a growing body of literature suggests that epigenetic changes may be involved in the development of MS, possibly by mediating the effects of environmental risk factors, such as smoking, vitamin D deficiency and Epstein-Barr virus infection. Such studies are also beginning to deliver important insights into the pathophysiology of MS. For example, inflammation and demyelination in relapsing-remitting MS may be related to the increased differentiation of T cells toward a T-helper 17 phenotype, which is an important epigenetically regulated pathophysiological mechanism. In progressive MS, other epigenetically regulated mechanisms, such as increased histone acetylation and citrullination of myelin basic protein, might exacerbate the disease course. In this Review, we summarize current knowledge on the role of epigenetic changes in the pathophysiology of MS.
authors.affiliation: Department of Clinical Neurosciences, University of Calgary, Foothills Hospital, 1403-29th Street N. W., Calgary, AB T2N 2T9, Canada. mwkoch@ucalgary.ca
authors.forename: Marcus W
authors.initials: MW
authors.lastname: Koch
authors.forename: Luanne M
authors.initials: LM
authors.lastname: Metz
authors.forename: Olga
authors.initials: O
authors.lastname: Kovalchuk
mesh_terms: D002956:Citrulline / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D018450:Disease Progression; D044127:Epigenesis, Genetic / Q000235:genetics*; D005544:Forecasting; D059647:Gene-Environment Interaction; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D004676:Myelin Basic Protein / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D009841:Oligonucleotides / Q000627:therapeutic use; D012307:Risk Factors; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D056572:Histone Deacetylase Inhibitors; D018836:Inflammation Mediators; D004676:Myelin Basic Protein; D018377:Neurotransmitter Agents; D009841:Oligonucleotides; C477371:locked nucleic acid; D002956:Citrulline