Epigenetic mechanisms in neuroinflammatory disease of the brain: Multiple sclerosis.

Abstract

Multiple sclerosis (MS) is a leading cause of lifelong incurable progressive disability in young adults that results in fatigue and accumulation of physical and cognitive disability. MS is characterized by autoimmune destruction of the myelin and subsequent neuroaxonal loss. The disease is triggered by environmental factors in genetically predisposed individuals. In this chapter, we review the key findings from epigenetic studies, with a focus on the most studied modification, that is, DNA methylation. Utilization of causal analytic approaches in large cohorts provides evidence that DNA methylation mediates genetic risk in MS. Complementary genome-wide DNA methylation studies in immune cells and brain samples of people with MS highlight methylome imprints, particularly in B lymphocytes, myeloid and nervous system cells, resulting from a net effect of multiple internal and external factors. Moreover, a subtle but distinct epigenetic signature of immune cells related to neural processes is starting to emerge in association with disease progression. The outcomes of epigenetic studies provide complementary mechanistic insights into the disease initiation and progression, and might aid a better understanding of the mechanisms underpinning the disease trajectory, development of novel diagnostic and prognostic biomarkers, and ultimately improving the care of people with MS.