Epigenetics of Multiple Sclerosis: An Updated Review

Abstract

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease characterized with autoimmune response against myelin proteins and progressive axonal loss. The heterogeneity of the clinical course and low concordance rates in monozygotic twins have indicated the involvement of complex heritable and environmental factors in MS pathogenesis. MS is more often transmitted to the next generation by mothers than fathers suggesting an epigenetic influence. One of the possible reasons of this parent-of-origin effect might be the human leukocyte antigen-DRB1*15 allele, which is the major risk factor for MS and regulated by epigenetic mechanisms such as DNA methylation and histone deacetylation. Moreover, major environmental risk factors for MS, vitamin D deficiency, smoking and Ebstein-Barr virus are all known to exert epigenetic changes. In the last few decades, compelling evidence implicating the role of epigenetics in MS has accumulated. Increased or decreased acetylation, methylation and citrullination of genes regulating the expression of inflammation and myelination factors appear to be particularly involved in the epigenetics of MS. Although much less is known about epigenetic factors causing neurodegeneration, epigenetic mechanisms regulating axonal loss, apoptosis and mitochondrial dysfunction in MS are in the process of identification. Additionally, expression levels of several microRNAs (miRNAs) (e.g., miR-155 and miR-326) are increased in MS brains and potential mechanisms by which these factors might influence MS pathogenesis have been described. Certain miRNAs may also be potentially used as diagnostic biomarkers in MS. Several reagents, especially histone deacetylase inhibitors have been shown to ameliorate the symptoms of experimental allergic encephalomyelitis. Ongoing efforts in this field are expected to result in characterization of epigenetic factors that can be used in prediction of treatment responsive MS patients, diagnostic screening panels and treatment methods with specific mechanism of action.

Global methylation status of sperm DNA in carriers of chromosome structural aberrations

“…Indeed, we cannot exclude the fact that the global methylation pattern in different abnormalities/diseases might future determinate the initial symptoms of ailing humans. In addition, the results of the methylation analysis for selected genes showed that the inheritance of affected DNA methylation patterns is a likely etiological candidate for many heritable disorders that were previously considered idiopathic 48495051…”

Management of women with multiple sclerosis through pregnancy and after childbirth

“…Genetic risk MS is a complex disease involving interactions between environmental and genetic factors, with epigenetic mechanisms likely involved [Harbo et al 2013;Küçükali et al 2015]. Patients are concerned about risk to their children.…”

Differential upregulation of the hypothetical transmembrane protein 66 (TMEM66) in multiple sclerosis patients with potential inflammatory response

“…Various genetic, immunological and environmental factors have been associated with inducing the onset and progression of the disease (1)(2)(3). Genetics may play a role in the disease pathogenesis as MS is more common in the Caucasian population and the frequency of MS appears to increase with the distance from the Equator in the two hemispheres (4).…”