title: Epigenetic Modifications and Therapy in Multiple Sclerosis.
abstract: Breakthroughs in genetic studies, like whole human genome sequencing and genome-wide association studies (GWAS), have richened our knowledge of etiopathology of autoimmune diseases (AID) through discovery of genetic patterns. Nonetheless, the precise etiology of autoimmune diseases remains largely unknown. The lack of complete concordance of autoimmune disease in identical twins suggests that non-genetic factors also play a major role in determining disease susceptibility. Although there is no certain definition, epigenetics has been known as heritable alterations in gene function without changes in the nucleotide sequence. DNA methylation, histone modifications, and microRNA-associated gene expression suppression are the central mechanisms for epigenetic regulations. Multiple sclerosis (MS) is a disorder of the central nervous system (CNS), characterized by both inflammatory and neurodegenerative features. Although studies on epigenetic alterations in MS only began in the past decade, a mounting number of surveys suggest that epigenetic changes may be involved in the initiation and development of MS, probably through bridging the effects of environmental risk factors to genetics. Arming with clear understanding of epigenetic dysregulations underpins development of epigenetic therapies. Identifying agents inhibiting the enzymes controlling epigenetic modifications, particularly DNA methyltransferases and histone deacetylases, will be promising therapeutic tool toward MS. In the article underway, it is aimed to go through the recent progresses, attempting to disclose how epigenetics associates with the pathogenesis of MS and how can be used as therapeutic approach.
authors.affiliation: Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Aslani
authors.affiliation: Markey Cancer Center, University of Kentucky, 741 South Limestone St. Biomedical Biological Research Building (BBSRB), 378D, Lexington, KY, 40506, USA. naser.jafari@uky.edu.
authors.forename: Naser
authors.initials: N
authors.lastname: Jafari
authors.affiliation: Department of Immunology, Faculty of Medicine, Zabol University of Medical Sciences, Zabol, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Javan
authors.affiliation: Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Jafar
authors.initials: J
authors.lastname: Karami
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Ahmadi
authors.affiliation: Department of Pharmacology, School of Medicine, Ardabil University of Medical Science, Ardabil, Iran.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Jafarnejad
mesh_terms: D000818:Animals; D019175:DNA Methylation; D004200:Diseases in Twins / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000628:therapy; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use; D055106:Genome-Wide Association Study; D042421:Histone Code; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D009103:Multiple Sclerosis / Q000235:genetics* / Q000628:therapy; D012307:Risk Factors
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D035683:MicroRNAs
keywords: Environmental factors; Epigenetic regulation; Epigenetic therapy; Multiple sclerosis