Tehran University Medical Journal (Mar 2020)
The function of epigenetic processes in multiple sclerosis: review article
Abstract
Multiple Sclerosis (MS) is a chronic neurological and inflammatory disorder that affects the nervous system. The etiology of MS is unknown, but genetic and environmental factors are involved in its pathogenesis. There is increasing evidence suggesting the role of epigenetic mechanisms in the pathogenesis of multiple sclerosis. Lack of vitamin D, smoking, and Epstein barr virus can cause epigenetic changes. Several studies have found that Dysregulation in DNA methylation is related to abnormal immune responses and post-translation modifications of myelin proteins in the brain specimens of MS patients. Molecular mechanisms through environmental signals lead to gene expression changes include DNA methylation, post modification of nucleosomal histones and non-coding RNAs. Also, abnormal microRNA profiles have been reported in the brain tissues and peripheral immune blood cells of MS patients. Increased histone acetylation and citrullination of myelin basic protein are two epigenetic mechanisms that may intensify the disease course, in the progressive type. The activation of T cells by histone deacetylase (HDAC) may contribute to the pathogenesis of MS disease and increase the intensity of disease. Increased of HDAC transcripts can also be observed during immune cell activation. Th1 differentiation is produced by HDACs, and the inhibition of these enzymes reduces the production of IFN-γ. The expression of 364 miRNA in peripheral blood mononuclear cell (PBMC) has been reported in the patients with remitting and relapsing and increased miR-18b and miR-599 regulation in the relapsing course. Expression of miRNAs in astrocytes, microglia, and CD8+ T cells also increased. The role of epigenome in this disease can be deduced from epidemiological studies of the geographical location influence, a month of birth, nutritional status (food and vitamin D absorption), and smoking. Despite of the ever-increasing advances, the epigenetic mechanisms of MS are still unknown. Numerous studies are needed to treat and control the disease and discover new and effective drugs due to the complexity of multiple sclerosis and the importance of epigenetic changes in multiple signaling pathways and the molecular mechanisms of different types of MS.
