Abstract
Melatonin is a hormone produced in and secreted by the pineal gland. Besides its role in regulating circadian rhythms, melatonin has a wide range of protective functions in the central nervous system (CNS) disorders. The mechanisms underlying this protective function are associated with the regulatory effects of melatonin on related genes and proteins. In addition to messenger ribonucleic acid (RNA) that can be translated into protein, an increasing number of non-coding RNAs in the human body are proven to participate in many diseases. This review discusses the current progress of research on the effects of melatonin modulation of non-coding RNAs (ncRNAs), including microRNA, long ncRNA, and circular RNA. The role of melatonin in regulating common pathological mechanisms through these ncRNAs is also summarized. Furthermore, the ncRNAs, currently shown to be involved in melatonin signaling in CNS diseases, are discussed. The information compiled in this review will open new avenues for future research into melatonin mechanisms and provide a further understanding of ncRNAs in the CNS.
Keywords: Central nervous system (CNS), circRNA, lncRNA, melatonin, microRNA, non-coding RNA (ncRNA).
Graphical Abstract
[http://dx.doi.org/10.2174/1570159X14666161228122115] [PMID: 28503116]
[http://dx.doi.org/10.1210/er.2018-00084] [PMID: 30215696]
[http://dx.doi.org/10.1111/jpi.12264] [PMID: 26201382]
[http://dx.doi.org/10.1007/s12975-017-0559-x] [PMID: 28766251]
[http://dx.doi.org/10.1097/00004647-199905000-00005] [PMID: 10326718]
[http://dx.doi.org/10.2174/1570159X15666170313123454] [PMID: 28294066]
[http://dx.doi.org/10.2741/4217] [PMID: 24389194]
[http://dx.doi.org/10.1038/nature11247] [PMID: 22955616]
[http://dx.doi.org/10.1038/nature11233] [PMID: 22955620]
[http://dx.doi.org/10.1152/physrev.00041.2015] [PMID: 27535639]
[http://dx.doi.org/10.1016/j.tem.2018.03.008] [PMID: 29631868]
[http://dx.doi.org/10.1093/carcin/bgx026] [PMID: 28449079]
[http://dx.doi.org/10.1016/j.molmed.2017.11.003] [PMID: 29246760]
[http://dx.doi.org/10.1016/j.omtn.2017.07.014] [PMID: 28918050]
[http://dx.doi.org/10.14336/AD.2018.0409] [PMID: 31011481]
[http://dx.doi.org/10.1016/j.biopha.2017.07.010] [PMID: 28724215]
[http://dx.doi.org/10.3390/ijms19092687] [PMID: 30201903]
[http://dx.doi.org/10.18632/oncotarget.19316] [PMID: 29137263]
[http://dx.doi.org/10.1016/S0092-8674(04)00045-5] [PMID: 14744438]
[http://dx.doi.org/10.1016/0092-8674(93)90529-Y] [PMID: 8252621]
[http://dx.doi.org/10.1016/j.pneurobio.2017.08.002] [PMID: 28842356]
[http://dx.doi.org/10.1007/s12975-014-0364-8] [PMID: 25127724]
[http://dx.doi.org/10.1177/0271678X18773871] [PMID: 29708005]
[http://dx.doi.org/10.1161/CIRCRESAHA.117.311572] [PMID: 28724745]
[http://dx.doi.org/10.1007/s12975-017-0520-z] [PMID: 28101763]
[http://dx.doi.org/10.1089/neu.2017.5111] [PMID: 28762893]
[http://dx.doi.org/10.3389/fnmol.2017.00183] [PMID: 28642684]
[http://dx.doi.org/10.1038/nbt.3835] [PMID: 28398344]
[http://dx.doi.org/10.15252/embj.201387576] [PMID: 25001178]
[http://dx.doi.org/10.1038/nrneurol.2015.57] [PMID: 25896087]
[http://dx.doi.org/10.1016/j.pneurobio.2017.07.005] [PMID: 28779869]
[PMID: 28676013]
[http://dx.doi.org/10.3171/2015.1.JNS141577] [PMID: 26230475]
[http://dx.doi.org/10.1007/s12035-014-8993-1] [PMID: 25416859]
[http://dx.doi.org/10.1016/j.canlet.2014.10.003] [PMID: 25305447]
[http://dx.doi.org/10.2174/1570159X14666160630210422] [PMID: 27397479]
[http://dx.doi.org/10.1016/j.neuron.2015.09.045] [PMID: 26637795]
[http://dx.doi.org/10.1038/s41419-018-0282-x] [PMID: 29449542]
[http://dx.doi.org/10.1016/j.neuron.2014.12.024] [PMID: 25556833]
[http://dx.doi.org/10.1083/jcb.141.7.1601] [PMID: 9647652]
[http://dx.doi.org/10.1161/STROKEAHA.118.021010] [PMID: 30571439]
[http://dx.doi.org/10.1186/s12974-018-1240-3] [PMID: 30001722]
[http://dx.doi.org/10.1186/s12943-018-0812-2] [PMID: 29458374]
[http://dx.doi.org/10.1126/science.aaf6260] [PMID: 27540166]
[http://dx.doi.org/10.1126/science.aag2590] [PMID: 27540165]
[http://dx.doi.org/10.1038/nm.2399] [PMID: 21738161]
[http://dx.doi.org/10.2174/1570159X16666180302115544] [PMID: 29512465]
[http://dx.doi.org/10.1016/j.pneurobio.2017.03.004] [PMID: 28322921]
[http://dx.doi.org/10.1038/nm.4397] [PMID: 28886007]
[http://dx.doi.org/10.1038/nm.2266] [PMID: 21131957]
[http://dx.doi.org/10.1523/JNEUROSCI.0600-12.2013] [PMID: 23516279]
[http://dx.doi.org/10.1080/15548627.2018.1522467] [PMID: 30208760]
[http://dx.doi.org/10.1007/s00401-017-1803-x] [PMID: 29302779]
[http://dx.doi.org/10.1038/ncomms5386] [PMID: 25019481]
[http://dx.doi.org/10.1038/ncomms2801] [PMID: 23612311]
[http://dx.doi.org/10.1155/2013/186872] [PMID: 23762086]
[http://dx.doi.org/10.1016/j.pneurobio.2016.01.005] [PMID: 26851161]
[http://dx.doi.org/10.1186/s12974-019-1464-x] [PMID: 30961627]
[http://dx.doi.org/10.1186/s12974-018-1139-z] [PMID: 29636074]
[http://dx.doi.org/10.1111/jpi.12354] [PMID: 27441728]
[http://dx.doi.org/10.1111/jpi.12525] [PMID: 30242884]
[http://dx.doi.org/10.2174/157015908785777201] [PMID: 19506721]
[http://dx.doi.org/10.1002/jcp.26843] [PMID: 29995978]
[http://dx.doi.org/10.1002/jcb.26700] [PMID: 29369410]
[http://dx.doi.org/10.1002/jcb.29108] [PMID: 31190362]
[http://dx.doi.org/10.1007/s12035-018-1299-y] [PMID: 30143969]
[http://dx.doi.org/10.1016/j.brainres.2014.09.055] [PMID: 25280466]
[http://dx.doi.org/10.1007/s12035-016-9842-1] [PMID: 27023223]
[http://dx.doi.org/10.3892/or.2017.5780] [PMID: 28677777]
[http://dx.doi.org/10.1111/jpi.12331] [PMID: 27062045]
[http://dx.doi.org/10.1002/biof.1411] [PMID: 29322615]
[http://dx.doi.org/10.1155/2019/4087298] [PMID: 30755784]
[http://dx.doi.org/10.1038/cddis.2016.210] [PMID: 27512954]
[http://dx.doi.org/10.1523/JNEUROSCI.1260-14.2014] [PMID: 25057207]
[http://dx.doi.org/10.1002/glia.22404] [PMID: 22907769]
[http://dx.doi.org/10.1016/j.tcb.2011.04.001] [PMID: 21550244]
[http://dx.doi.org/10.1111/jpi.12278] [PMID: 26383078]
[http://dx.doi.org/10.1089/dna.2017.4040] [PMID: 29359963]
[http://dx.doi.org/10.1038/cdd.2008.150] [PMID: 18846107]
[http://dx.doi.org/10.1111/jpi.12414] [PMID: 28398673]
[http://dx.doi.org/10.1111/jpi.12449] [PMID: 29024030]
[http://dx.doi.org/10.1038/cddis.2017.58] [PMID: 28252651]
[http://dx.doi.org/10.1111/jpi.12503] [PMID: 29770487]
[http://dx.doi.org/10.3389/fimmu.2019.01360] [PMID: 31258534]
[http://dx.doi.org/10.1016/j.trsl.2015.04.002] [PMID: 25936762]
[http://dx.doi.org/10.1016/j.redox.2017.11.025] [PMID: 29248830]
[http://dx.doi.org/10.1038/s41418-017-0019-x] [PMID: 29229992]
[PMID: 28405617] [http://dx.doi.org/10.1172/jci.insight.90777]
[http://dx.doi.org/10.1038/mp.2017.171] [PMID: 28886009]
[http://dx.doi.org/10.1016/j.bbadis.2019.05.009] [PMID: 31102787]
[http://dx.doi.org/10.1038/s41418-017-0053-8] [PMID: 29348676]
[http://dx.doi.org/10.1111/jpi.12534] [PMID: 30329173]
[http://dx.doi.org/10.1007/s12264-015-1545-5] [PMID: 26254059]
[http://dx.doi.org/10.1016/j.jneuroim.2015.01.012] [PMID: 25773147]
[http://dx.doi.org/10.1002/jcp.26498] [PMID: 29380367]
[http://dx.doi.org/10.12659/MSM.900218] [PMID: 28365714]
[http://dx.doi.org/10.1080/15548627.2019.1569947] [PMID: 30654687]
[http://dx.doi.org/10.1186/s13045-018-0619-z] [PMID: 29866190]
[http://dx.doi.org/10.3390/cells8091053] [PMID: 31500354]
[http://dx.doi.org/10.1007/s12035-012-8355-9] [PMID: 23054680]
[http://dx.doi.org/10.1111/j.1600-079X.2004.00136.x] [PMID: 15298664]
[http://dx.doi.org/10.1111/jpi.12552] [PMID: 30618087]
[http://dx.doi.org/10.1074/jbc.M112.356733] [PMID: 22908386]
[http://dx.doi.org/10.1016/j.brainres.2017.05.001] [PMID: 28502584]
[http://dx.doi.org/10.1038/s41419-018-1089-5] [PMID: 30305621]
[http://dx.doi.org/10.1038/s41598-017-02152-x] [PMID: 28522826]
[http://dx.doi.org/10.1016/j.molcel.2010.02.018] [PMID: 20227367]
[http://dx.doi.org/10.4161/cc.9.14.12248] [PMID: 20647762]
[http://dx.doi.org/10.1016/j.molcel.2007.07.015] [PMID: 17679093]
[http://dx.doi.org/10.3389/fncel.2015.00193] [PMID: 26041995]
[http://dx.doi.org/10.1161/STROKEAHA.111.000613] [PMID: 23696548]
[http://dx.doi.org/10.1016/j.biomaterials.2016.03.025] [PMID: 27031810]
[http://dx.doi.org/10.1016/j.biopsych.2017.07.023] [PMID: 28965984]
[http://dx.doi.org/10.1016/j.jconrel.2016.06.005] [PMID: 27269730]
[http://dx.doi.org/10.1111/bpa.12267] [PMID: 25976060]
[http://dx.doi.org/10.1007/s11064-018-02714-z] [PMID: 30628018]
[http://dx.doi.org/10.4103/1673-5374.156983] [PMID: 26330841]
[http://dx.doi.org/10.1016/j.nano.2015.10.011] [PMID: 26582736]
[http://dx.doi.org/10.1016/j.molmed.2017.07.005] [PMID: 28811172]
[http://dx.doi.org/10.1016/j.pneurobio.2013.11.002] [PMID: 24269804]
[http://dx.doi.org/10.1038/emm.2017.48] [PMID: 28524176]
[http://dx.doi.org/10.4103/1673-5374.135333] [PMID: 25206789]
[http://dx.doi.org/10.1016/j.celrep.2016.02.042] [PMID: 26947066]
[http://dx.doi.org/10.3892/ijmm.2013.1365] [PMID: 23624869]
[http://dx.doi.org/10.1007/s10072-014-1895-1] [PMID: 25112530]
[http://dx.doi.org/10.3892/ijmm.2017.3088] [PMID: 28791348]
[http://dx.doi.org/10.1038/onc.2014.168] [PMID: 24954504]
[http://dx.doi.org/10.1186/s12943-018-0911-0] [PMID: 30470262]
[http://dx.doi.org/10.1073/pnas.0605298103] [PMID: 16885212]
[http://dx.doi.org/10.1002/emmm.201202318] [PMID: 23733368]
[http://dx.doi.org/10.1034/j.1600-079X.2003.00046.x] [PMID: 12662353]
[http://dx.doi.org/10.1111/j.1600-079X.2008.00591.x] [PMID: 18410310]
[http://dx.doi.org/10.1371/journal.pone.0166688] [PMID: 27846323]
[http://dx.doi.org/10.1016/j.neurobiolaging.2010.04.034] [PMID: 20619502]
[http://dx.doi.org/10.1111/cas.12351] [PMID: 24418124]
[http://dx.doi.org/10.3892/mmr.2016.5460] [PMID: 27430517]
[http://dx.doi.org/10.1095/biolreprod.115.138313] [PMID: 27465135]
[http://dx.doi.org/10.1073/pnas.0801613105] [PMID: 18755897]
[http://dx.doi.org/10.1016/j.jhep.2012.08.008] [PMID: 22902550]
[http://dx.doi.org/10.3892/ijmm.2016.2775] [PMID: 27748823]
[http://dx.doi.org/10.1111/jpi.12193] [PMID: 25401748]
[http://dx.doi.org/10.1111/cns.12588] [PMID: 27421686]
[http://dx.doi.org/10.1007/s12035-016-9776-7] [PMID: 26867656]
[http://dx.doi.org/10.1111/jpi.12434] [PMID: 28708259]
[http://dx.doi.org/10.3892/or.2013.2685] [PMID: 23970205]
[http://dx.doi.org/10.1210/jc.2010-0581] [PMID: 20668041]
[http://dx.doi.org/10.3389/fimmu.2017.01520] [PMID: 29176977]
[http://dx.doi.org/10.1002/ana.23967] [PMID: 23818336]
[http://dx.doi.org/10.1073/pnas.0610731104] [PMID: 17242365]
[http://dx.doi.org/10.1111/jpi.12547] [PMID: 30597604]
[http://dx.doi.org/10.1007/s00401-016-1605-6] [PMID: 27497943]
[http://dx.doi.org/10.1002/ana.24304] [PMID: 25381879]
[http://dx.doi.org/10.1186/s12974-016-0753-x] [PMID: 27829437]
[http://dx.doi.org/10.1093/hmg/ddu348] [PMID: 24990149]
[http://dx.doi.org/10.1093/hmg/ddt164] [PMID: 23585551]
[http://dx.doi.org/10.15252/emmm.201606520] [PMID: 27485122]
[http://dx.doi.org/10.1021/acschemneuro.8b00460] [PMID: 30817108]
[http://dx.doi.org/10.3389/fnmol.2018.00471] [PMID: 30618618]
[http://dx.doi.org/10.1016/j.expneurol.2019.03.017] [PMID: 30930097]
[http://dx.doi.org/10.1016/j.neuint.2016.11.011] [PMID: 27940326]
[http://dx.doi.org/10.1080/21691401.2019.1610414] [PMID: 31062615]
[PMID: 25126160]
[http://dx.doi.org/10.1155/2016/5108489] [PMID: 27579184]
[http://dx.doi.org/10.1016/j.brainres.2015.06.046] [PMID: 26168887]
[http://dx.doi.org/10.1111/jpi.12432] [PMID: 28658519]
[http://dx.doi.org/10.1038/ncb2521] [PMID: 22684254]
[http://dx.doi.org/10.1016/j.cell.2009.01.002] [PMID: 19167326]
[http://dx.doi.org/10.1038/s41419-017-0155-8] [PMID: 29367587]
[http://dx.doi.org/10.1016/j.omtn.2018.08.015] [PMID: 30240970]
[PMID: 27981546]
[http://dx.doi.org/10.1371/journal.pone.0086295] [PMID: 24466011]
[http://dx.doi.org/10.1111/jpi.12170] [PMID: 25163989]
[http://dx.doi.org/10.1146/annurev.neuro.24.1.677] [PMID: 11520916]
[http://dx.doi.org/10.1073/pnas.1411674111] [PMID: 25205808]
[http://dx.doi.org/10.1093/neuonc/not107] [PMID: 24092860]
[http://dx.doi.org/10.1073/pnas.73.11.3852] [PMID: 1069269]
[http://dx.doi.org/10.1371/journal.pgen.1003777] [PMID: 24039610]
[http://dx.doi.org/10.1038/s41576-019-0158-7] [PMID: 31395983]
[http://dx.doi.org/10.1016/j.molcel.2015.03.027] [PMID: 25921068]
[http://dx.doi.org/10.1007/s12264-019-00361-0] [PMID: 30887246]
[http://dx.doi.org/10.1161/STROKEAHA.117.017469] [PMID: 28701578]
[PMID: 31502677]
[http://dx.doi.org/10.1080/15548627.2018.1458173] [PMID: 29938598]
[http://dx.doi.org/10.1523/JNEUROSCI.0299-19.2019] [PMID: 31311824]
[http://dx.doi.org/10.3389/fbioe.2019.00222] [PMID: 31572720]
[http://dx.doi.org/10.1038/s41593-019-0501-5] [PMID: 31591557]
[http://dx.doi.org/10.1016/j.expneurol.2018.12.003] [PMID: 30529438]
[http://dx.doi.org/10.1089/neu.2017.5468] [PMID: 29357736]
[http://dx.doi.org/10.3389/fgene.2016.00053] [PMID: 27092176]
[http://dx.doi.org/10.1016/j.omtn.2018.11.014] [PMID: 30623853]
[http://dx.doi.org/10.1186/s12943-018-0933-7] [PMID: 30621700]
[http://dx.doi.org/10.1111/jcmm.13587] [PMID: 29532994]
[http://dx.doi.org/10.1038/s41419-018-0852-y] [PMID: 30082829]
[http://dx.doi.org/10.1038/s41586-019-1191-6] [PMID: 31068698]
[http://dx.doi.org/10.1016/j.brainres.2019.146401] [PMID: 31445031]
[http://dx.doi.org/10.1016/j.freeradbiomed.2012.01.030] [PMID: 22330064]
[http://dx.doi.org/10.1016/j.neulet.2013.02.073] [PMID: 23562888]
[http://dx.doi.org/10.1016/j.lfs.2014.01.085] [PMID: 24530291]
[http://dx.doi.org/10.1016/j.neuro.2016.09.002] [PMID: 27620136]
[http://dx.doi.org/10.1016/j.redox.2017.04.006] [PMID: 28395173]
[http://dx.doi.org/10.3389/fphar.2019.00297] [PMID: 31024297]
[http://dx.doi.org/10.1016/j.neuint.2016.12.011] [PMID: 28012846]
[http://dx.doi.org/10.3892/ijmm.2018.3607] [PMID: 29620280]
[http://dx.doi.org/10.1111/jpi.12395] [PMID: 28178380]
[http://dx.doi.org/10.1016/j.biopha.2018.09.077] [PMID: 30245469]
[http://dx.doi.org/10.3389/fnins.2018.00638] [PMID: 30283292]
[http://dx.doi.org/10.1111/jpi.12300] [PMID: 26639408]
[http://dx.doi.org/10.1038/s41598-017-02679-z] [PMID: 28546552]
[http://dx.doi.org/10.3389/fnmol.2018.00093] [PMID: 29632474]
[http://dx.doi.org/10.1111/jpi.12337] [PMID: 27117839]
[http://dx.doi.org/10.1111/jpi.12344] [PMID: 27159133]
[http://dx.doi.org/10.1016/j.neuint.2015.10.008] [PMID: 26527380]
[PMID: 26523219]
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.12.014] [PMID: 30553970]
[http://dx.doi.org/10.3390/cells8070760] [PMID: 31330909]
[http://dx.doi.org/10.1371/journal.pone.0154427] [PMID: 27152411]
[http://dx.doi.org/10.1007/s12035-016-0131-9] [PMID: 27686077]
[http://dx.doi.org/10.1007/s11064-017-2251-7] [PMID: 28417262]
[http://dx.doi.org/10.1111/and.12692] [PMID: 27595881]
[http://dx.doi.org/10.1002/jnr.23930] [PMID: 27717042]
[http://dx.doi.org/10.1111/jpi.12311] [PMID: 26762966]
[http://dx.doi.org/10.1002/jnr.24409] [PMID: 31006904]
[http://dx.doi.org/10.1002/jcb.27794] [PMID: 30257055]
[http://dx.doi.org/10.1007/s11064-019-02838-w] [PMID: 31325156]
[http://dx.doi.org/10.1016/j.lfs.2017.11.016] [PMID: 29138117]
[http://dx.doi.org/10.1080/15548627.2015.1082020] [PMID: 26292069]
[http://dx.doi.org/10.4103/0366-6999.218025] [PMID: 29133763]
[http://dx.doi.org/10.3109/10715762.2015.1027198] [PMID: 25791066]
[http://dx.doi.org/10.1111/jpi.12415] [PMID: 28423196]
[http://dx.doi.org/10.1111/jpi.12343] [PMID: 27159033]
[http://dx.doi.org/10.3233/JAD-150161] [PMID: 26402759]
[http://dx.doi.org/10.1111/jpi.12248] [PMID: 25988948]
[http://dx.doi.org/10.1111/jphp.12830] [PMID: 28994117]
[http://dx.doi.org/10.1021/cn5002073] [PMID: 25393881]
[http://dx.doi.org/10.1111/jpi.12194] [PMID: 25401971]
[PMID: 31081111]
[http://dx.doi.org/10.1016/j.neulet.2019.134376] [PMID: 31325578]
[http://dx.doi.org/10.1111/jpi.12578] [PMID: 30943316]
[http://dx.doi.org/10.1111/jpi.12200] [PMID: 25491598]
[http://dx.doi.org/10.1111/iep.12122] [PMID: 25891353]
[http://dx.doi.org/10.1111/jpi.12182] [PMID: 25251028]
[http://dx.doi.org/10.1007/s11481-018-9824-3] [PMID: 30478761]
[http://dx.doi.org/10.3389/fnagi.2017.00165] [PMID: 28596733]
[http://dx.doi.org/10.1186/s12967-015-0454-8] [PMID: 25889845]
[http://dx.doi.org/10.1111/jpi.12556] [PMID: 30648757]
[http://dx.doi.org/10.1111/j.1600-079X.2012.00985.x] [PMID: 22404622]
[http://dx.doi.org/10.1016/j.canlet.2009.06.016] [PMID: 19632770]
[http://dx.doi.org/10.1111/jpi.12052] [PMID: 23551342]