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Review
. 2017;958:65-90.
doi: 10.1007/978-3-319-47861-6_6.

Molecular Genetic and Epigenetic Basis of Multiple Sclerosis

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Review

Molecular Genetic and Epigenetic Basis of Multiple Sclerosis

Zohreh Hojati. Adv Exp Med Biol. .

Abstract

Multiple Sclerosis (MS) is a chronic immune-mediated disease of spinal cord and brain. The initial event in MS occurs when activated CD4+ T cells in periphery exacerbates immune responses by stimulating immune cells such as B cells, CD8+ cells, mast cells, granulocytes and monocytes. These proinflammatory cells pass blood brain barrier by secreting proinflammatory cytokines including TNF-α and INF-γ which activate adhesion factors. APCs (antigen-presenting cells) reactivate CD4+ T cells after infiltrating the CNS and CD4+ T cells produce cytokines and chemokines. These proinflammatory cytokines aggravate inflammation by inducing myelin phagocytosis through microglia and astrocytes activation. MS is believed to have a multifactorial origin that includes a combination of multiple genetic, environmental and stochastic factors. Although the exact component of MS risks that can be explained by these factors is difficult to determine, estimates based on genetic and epidemiological studies suggest that up to 60-70 % of the total risk of MS may be contribute to genetic factors. In continue, firstly we provide an overview of the current understanding of epigenetic mechanisms, and so present evidence of how the epigenetic modifications contribute to increased susceptibility of MS. We also explain how specified epigenetic modifications may influence the pathophysiology and key aspects of disease in MS (demyelination, remyelination, inflammation, and neurodegeneration). Finally, we tend to discuss how environmental factors and epigenetic mechanisms may interact to have an effect on MS risk and clinical outcome and recommend new therapeutic interventions that might modulate patients' epigenetic profiles.

Keywords: Epigenetic basis; Experimental autoimmune encephalomyelitis; Multiple sclerosis.

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