Abstract
Multiple sclerosis (MS) is an autoimmune inflammatory and neurodegenerative disease of the central nervous system that involves several not yet fully elucidated pathophysiologic mechanisms. There is increasing evidence that epigenetic modifications at level of DNA bases, histones, and micro-RNAs may confer risk for MS. DNA methylation seems to have a prominent role in the epigenetics of MS, as aberrant methylation in the promoter regions across genome may underlie several processes involved in the initiation and development of MS. In the present review, we discuss current understanding regarding the role of DNA methylation in MS, possible therapeutic implications and future emerging issues.
Highlights
Multiple sclerosis (MS) is an autoimmune inflammatory and neurodegenerative disease of the central nervous system that involves several not yet fully elucidated pathophysiologic mechanisms
DNA methylation seems to have a prominent role in the epigenetics of MS, as aberrant methylation in the promoter regions across genome may underlie several processes involved in the initiation and development of MS
We discuss current understanding regarding the role of DNA methylation in MS, possible therapeutic implications and future emerging issues
Summary
Autoimmun Highlights (2016) 7:12 diseases, such as systemic lupus erythematosus (SLE), cancer, rheumatoid arthritis (RA), and diabetes melitus type 1 (T1DM) [6,7,8]. DNA methylation is an essential process for normal cell development, proliferation, and genome integrity [21] It is mediated by a number of enzymes called DNA methyltransferases (DNMTs), the most important of which are DNMT1, DNMT3a, and DNMT3b. DNA methylation mainly occurs at regions where a guanine accompanies the cytosine, forming a dinucleotide Hundreds of these dinucleotides are found repetitively in gene promoters, as CpG islands. Hypermethylation of these sites leads to silencing of the gene, by not allowing transcription factors to bind to the gene promoter, while hypomethylation to the transcription and usually to the expression of the subjected gene [22] The demethylation of those regions can occur in either a passive or in an active way.
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