This review article from the US looks at the pathogenesis of MS which they propose involves the modulation of cellular mechanisms regulating gene expression, based on the integration of epidemiological data, genome-wide association studies and reports of neuroimaging abnormalities in clinically unaffected individuals.
Epigenetic mechanisms include post-translational modifications of nucleosomal histones, DNA methylation and regulation of non-coding miRNAs, which can be affected by environment, diet, smoking habits, exercise and drug addition. Environmental factors may regulate disease manifestation by modulating the epigenome, with MS resulting from cumulative changes imposed by environmental factors on the immune system.
The mix of epigenetic changes in immune cells and oligodendrocytes might modulate disease onset, by modulating expression of susceptibility genes and disease course, and by modulating myelin formation. Overall, the authors suggest further research is needed in single tissue, looking at epigenetic factors longitudinally to determine the effect of environmental factors on disease course and therapeutic responsiveness.
Authors: Huynh JL, Casaccia P
Source: Lancet Neurol. 2013 Feb;12(2):195-206
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