Abstract
Multiple Sclerosis (MS) is a multifactorial, neurodegenerative, and inflammatory demyelination disease with incomplete remyelination in the CNS. It would be more informative to reveal the underlying molecular mechanisms of MS. Molecular mechanisms involving epigenetic changes play a pivotal role in this disease. Epigenetic changes impact gene expression without altering the underlying DNA sequence. The main epigenetic modifications that play a key role in the regulation of gene expression principally include DNA methylation, histone modifications, and microRNA- associated post-transcriptional gene silencing. In this review, we summarize the dynamics of epigenetic changes and their relation to environmental risk factors in MS pathogenesis. Studies suggest that epigenetic changes have a role in the development of MS and environmental risk factors, such as vitamin D, smoking, and Epstein-Barr virus infection seem to influence the development and susceptibility to MS. Investigating epigenetic and environmental factors can provide new opportunities for the molecular basis of the diseases, which shows complicated pathogenesis. Epigenetic research has the potential to complete our understanding of MS initiation and progression. Increased understanding of MS molecular pathways leads to new insights into potential MS therapies. However, there is a need for in vivo evaluation of the role of epigenetic factors in MS therapy. It would be more valuable to indicate the role of various epigenetic factors in MS.
Keywords: Epigenetic mechanisms, multiple sclerosis, DNA methylation, histone modification, microRNAs, environmental risk factors.
[http://dx.doi.org/10.1016/j.msard.2019.101452] [PMID: 31670010]
[http://dx.doi.org/10.3390/biomedicines7030056] [PMID: 31362384]
[http://dx.doi.org/10.1101/cshperspect.a028928] [PMID: 29358317]
[http://dx.doi.org/10.1016/j.jaut.2015.06.010] [PMID: 26142251]
[http://dx.doi.org/10.1186/s40246-015-0041-3] [PMID: 26216216]
[http://dx.doi.org/10.3390/ijms22073696] [PMID: 33918133]
[http://dx.doi.org/10.3389/fonc.2019.01293] [PMID: 31850200]
[http://dx.doi.org/10.1016/j.arr.2021.101348] [PMID: 33930583]
[http://dx.doi.org/10.1038/npp.2012.112] [PMID: 22781841]
[http://dx.doi.org/10.3390/genes10020172] [PMID: 30813436]
[http://dx.doi.org/10.1007/978-1-4419-9967-2_1] [PMID: 22956494]
[http://dx.doi.org/10.1007/s00018-021-03927-2] [PMID: 34482420]
[http://dx.doi.org/10.3390/cells8101236] [PMID: 31614602]
[http://dx.doi.org/10.1002/jcp.24641] [PMID: 24700487]
[http://dx.doi.org/10.1038/s41598-019-45433-3] [PMID: 31217537]
[PMID: 30147811]
[http://dx.doi.org/10.32607/20758251-2016-8-3-103-110] [PMID: 27795849]
[http://dx.doi.org/10.1371/journal.pone.0206511] [PMID: 30379917]
[http://dx.doi.org/10.1177/1352458513516529] [PMID: 24336351]
[http://dx.doi.org/10.1007/s10735-018-9758-3] [PMID: 29455276]
[http://dx.doi.org/10.1177/1073858415574728] [PMID: 25717070]
[http://dx.doi.org/10.1002/ana.23860] [PMID: 23595422]
[http://dx.doi.org/10.1038/s41598-017-08623-5] [PMID: 28821749]
[http://dx.doi.org/10.1186/s12974-019-1667-1] [PMID: 31937331]
[http://dx.doi.org/10.1038/cr.2011.22] [PMID: 21321607]
[http://dx.doi.org/10.1038/s41392-019-0095-0] [PMID: 31871779]
[http://dx.doi.org/10.1007/s00018-008-8432-4] [PMID: 18985277]
[http://dx.doi.org/10.1007/978-94-007-4525-4_13] [PMID: 23150256]
[http://dx.doi.org/10.1016/j.joca.2011.12.012] [PMID: 22281264]
[http://dx.doi.org/10.1371/journal.pone.0050000] [PMID: 23185513]
[http://dx.doi.org/10.3390/ijms18071414] [PMID: 28671573]
[http://dx.doi.org/10.1016/j.jaut.2016.07.011] [PMID: 27528513]
[http://dx.doi.org/10.1007/s12038-020-00099-2] [PMID: 33184251]
[http://dx.doi.org/10.1007/s12640-014-9508-6] [PMID: 25516120]
[http://dx.doi.org/10.1042/BSR20202160] [PMID: 32815547]
[http://dx.doi.org/10.5402/2012/690901] [PMID: 22461998]
[http://dx.doi.org/10.1523/JNEUROSCI.4349-14.2015] [PMID: 26558787]
[http://dx.doi.org/10.3389/fimmu.2018.01377] [PMID: 29988529]
[http://dx.doi.org/10.1155/2013/172351] [PMID: 23983402]
[http://dx.doi.org/10.3389/fimmu.2021.593473] [PMID: 33968012]
[http://dx.doi.org/10.1007/s12017-014-8298-6] [PMID: 24652042]
[http://dx.doi.org/10.1089/ars.2012.5068] [PMID: 23473637]
[http://dx.doi.org/10.1111/joim.13045] [PMID: 32614160]
[http://dx.doi.org/10.7150/ijms.8647] [PMID: 24936144]
[http://dx.doi.org/10.3389/fgene.2013.00008] [PMID: 23386861]
[http://dx.doi.org/10.1038/ni.1798] [PMID: 19838199]
[http://dx.doi.org/10.1016/j.cca.2021.01.020] [PMID: 33545109]
[http://dx.doi.org/10.3390/ijms131013227] [PMID: 23202949]
[http://dx.doi.org/10.1038/srep34512] [PMID: 27694855]
[PMID: 23346094]
[http://dx.doi.org/10.3389/fimmu.2018.01256] [PMID: 29915595]
[http://dx.doi.org/10.1101/cshperspect.a028944] [PMID: 29735578]
[http://dx.doi.org/10.1002/acn3.50862] [PMID: 31392849]
[http://dx.doi.org/10.3389/fpsyt.2017.00047] [PMID: 28396640]
[http://dx.doi.org/10.1007/s40120-017-0086-4] [PMID: 29243029]
[http://dx.doi.org/10.3390/ijms21093102] [PMID: 32354174]
[http://dx.doi.org/10.1080/15592294.2016.1276681] [PMID: 28055298]
[PMID: 25071589]
[http://dx.doi.org/10.1177/1756285612447090] [PMID: 22783368]
[http://dx.doi.org/10.1177/1352458517738131] [PMID: 29307295]
[http://dx.doi.org/10.1212/WNL.0b013e3181e24124] [PMID: 20530326]
[http://dx.doi.org/10.3390/ijerph15051033] [PMID: 29883409]
[http://dx.doi.org/10.3390/ijms130911718] [PMID: 23109880]
[http://dx.doi.org/10.3390/cells9071711] [PMID: 32708794]
[http://dx.doi.org/10.1080/1354750X.2019.1610497] [PMID: 31018714]
[http://dx.doi.org/10.1186/s13072-019-0311-8] [PMID: 31711545]
[http://dx.doi.org/10.1186/s13148-017-0387-6] [PMID: 28824732]
[http://dx.doi.org/10.3390/ijms20236005] [PMID: 31795255]
[http://dx.doi.org/10.1016/j.ebiom.2019.07.006] [PMID: 31303497]
[http://dx.doi.org/10.3390/ijms131217210] [PMID: 23247283]
[http://dx.doi.org/10.1186/s13148-021-01018-4] [PMID: 33593402]
[http://dx.doi.org/10.1037/pha0000382] [PMID: 32658533]
[http://dx.doi.org/10.1038/s41598-017-14788-w] [PMID: 29109506]
[http://dx.doi.org/10.1016/j.molmed.2019.11.003] [PMID: 31862243]
[http://dx.doi.org/10.1038/cti.2014.25] [PMID: 25505955]
[http://dx.doi.org/10.1016/j.micinf.2011.07.007] [PMID: 21835261]
[http://dx.doi.org/10.3389/fimmu.2019.00695] [PMID: 31001286]
[http://dx.doi.org/10.1038/leu.2012.108] [PMID: 22614176]
[http://dx.doi.org/10.2174/1570159X13666150211001600] [PMID: 26813117]
[http://dx.doi.org/10.3390/ijms20092241] [PMID: 31067680]
[http://dx.doi.org/10.1177/1352458517737389] [PMID: 29307300]
[http://dx.doi.org/10.1038/s41598-017-09301-2] [PMID: 28821874]
[http://dx.doi.org/10.1371/journal.pone.0012132] [PMID: 20711463]
[http://dx.doi.org/10.4049/jimmunol.1303488] [PMID: 24842756]
[http://dx.doi.org/10.1002/acn3.152] [PMID: 25642434]
[http://dx.doi.org/10.3109/00207454.2012.678444] [PMID: 22463747]
[http://dx.doi.org/10.1172/JCI88415] [PMID: 28067667]
[http://dx.doi.org/10.1371/journal.pone.0124555] [PMID: 25938517]
[http://dx.doi.org/10.4049/jimmunol.1300351] [PMID: 23686497]
[http://dx.doi.org/10.1093/brain/awp300] [PMID: 19952055]
[http://dx.doi.org/10.1016/j.immuni.2016.05.015] [PMID: 27332731]
[http://dx.doi.org/10.1073/pnas.1615253114] [PMID: 28209777]
[http://dx.doi.org/10.1016/j.bbi.2017.03.008] [PMID: 28336414]
[http://dx.doi.org/10.1177/1352458511410342] [PMID: 21677024]
[http://dx.doi.org/10.1016/j.jns.2017.02.015] [PMID: 28196747]
[http://dx.doi.org/10.1084/jem.20070994] [PMID: 17967903]
[http://dx.doi.org/10.1002/eji.201646716] [PMID: 28102541]
[http://dx.doi.org/10.1186/s12974-020-01770-z] [PMID: 32375811]
[http://dx.doi.org/10.1371/journal.pone.0119681] [PMID: 25860354]
[http://dx.doi.org/10.1080/15321819.2019.1655649] [PMID: 31422745]
[http://dx.doi.org/10.3390/cells8060533] [PMID: 31167379]
[http://dx.doi.org/10.4172/2155-9899.1000400] [PMID: 27308096]
[http://dx.doi.org/10.1177/1352458518763094] [PMID: 29512406]
[http://dx.doi.org/10.1089/jir.2010.0115] [PMID: 21235411]
[http://dx.doi.org/10.2174/187153010791213029] [PMID: 20384573]
[http://dx.doi.org/10.1016/j.humimm.2020.02.009] [PMID: 32122685]
[http://dx.doi.org/10.3109/1547691X.2015.1089343] [PMID: 26507681]