Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system. MS likely results from a complex interplay between predisposing causal gene variants (the strongest influence coming from HLA class II locus) and environmental risk factors such as smoking, infectious mononucleosis, and lack of sun exposure/vitamin D. However, little is known about the mechanisms underlying MS development and progression. Moreover, the clinical heterogeneity and variable response to treatment represent additional challenges to a comprehensive understanding and efficient treatment of disease. Epigenetic processes, such as DNA methylation and histone posttranslational modifications, integrate influences from the genes and the environment to regulate gene expression accordingly. Studying epigenetic modifications, which are stable and reversible, may provide an alternative approach to better understand and manage disease. We here aim to review findings from epigenetic studies in MS and further discuss the challenges and clinical opportunities arising from epigenetic research, many of which apply to other diseases with similar complex etiology. A growing body of evidence supports a role of epigenetic processes in the mechanisms underlying immune pathogenesis and nervous system dysfunction in MS. However, disparities between studies shed light on the need to consider possible confounders and methodological limitations for a better interpretation of the data. Nevertheless, translational use of epigenetics might offer new opportunities in epigenetic-based diagnostics and therapeutic tools for a personalized care of MS patients.
Studies have revealed that dysregulation in gene expression is one of the main aspects of multiple sclerosis (MS) pathogenesis. Although the molecular pathways underlying the immunomodulatory role of vitamin D (VD) in MS is not completely elucidated, VD has more recently become a topic of interest in immune regulation and is widely administered to patients with MS as an immunomodulatory supplement. Long non-coding RNAs (lncRNAs) are known to play important roles in regulation of gene expression via different mechanisms. Given that VD-related genes are regulated by epigenetic mechanisms, here we aimed to evaluate the role of VD in combination with HOTAIR and ANRIL lncRNAs using in vivo, in vitro and in silico experiments in MS pathogenesis. Our data revealed that HOTAIR but not ANRIL lncRNA is probably involved in the pathogenesis of MS and experimental autoimmune encephalomyelitis through an unclear mechanism and it seems that by affecting the expression, inflammation and VD can influence HOTAIR-related mechanisms, which require further study.
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