Epigenetics of multiple sclerosis

Abstract

Multiple sclerosis (MS) is a complex disease characterized by autoimmune demyelination of the myelin sheath of the central nervous system. Varying degrees of disability result from disruptions in neural, physical, and psychological processes. No clear cause of MS has been identified, but specific genetic mutations and environmental effects have been established as factors in disease development. However, the low disease concordance rates and transmission disequilibrium observed in MS prevent genetic factors alone from explaining increased susceptibility. As a result, the involvement of epigenetics, or heritable changes in the genome that are not caused by alterations in the underlying DNA sequence, has been proposed to resolve these apparent discrepancies. This article focuses on recent research into three primary epigenetic mechanisms and their relation to MS susceptibility: DNA methylation, histone modifications, and post-transcriptional regulation of target genes by microRNA. These epigenetic phenomena interact with each other and environmental stimuli to produce disease. Promising experimental research has revealed that inhibitors of such epigenetic activity reduce disease phenotypes in animal models. In this article, ways in which epigenetic changes can induce MS development are described and prospective research avenues are proposed.
 
 Keywords: epigenetics; multiple sclerosis (MS); DNA methylation; histones; microRNA (miRNA)