Abstract
Alzheimer’s disease (AD) is a multifactorial disorder resulting from the complex interaction between genetic, epigenetic, and environmental factors. It represents an impending epidemic and lacks effective pharmacological interventions. The emergence of high throughput sequencing techniques and comprehensive genome evaluation has uncovered a diverse spectrum of noncoding RNA (ncRNA) families. ncRNAs are the critical modulators of an eclectic array of biological processes and are now transpiring as imperative players in diagnosing and treating various diseases, including neurodegenerative disorders. Several ncRNAs are explicitly augmented in the brain, wherein they potentially regulate cognitive abilities and other functions of the central nervous system. Growing evidence suggests the substantial role of ncRNAs as modulators of tau phosphorylation, Aβ production, neuroinflammation, and neuronal survival. It indicates their therapeutic relevance as a biomarker and druggable targets against AD. The current review summarizes the existing literature on the functional significance of ncRNAs in AD pathogenesis and its imminent implications in clinics.
Graphical Abstract
[http://dx.doi.org/10.1534/genetics.112.146704] [PMID: 23463798]
[http://dx.doi.org/10.3389/fgene.2015.00002] [PMID: 25674102]
[http://dx.doi.org/10.1515/jib-2019-0027] [PMID: 31301674]
[http://dx.doi.org/10.3390/ncrna4020015] [PMID: 29880782]
[http://dx.doi.org/10.3390/ncrna7010017] [PMID: 33668203]
[http://dx.doi.org/10.1016/j.biopha.2023.114672] [PMID: 37060662]
[http://dx.doi.org/10.1152/physrev.00041.2015] [PMID: 27535639]
[http://dx.doi.org/10.1002/cbf.3079] [PMID: 25475931]
[http://dx.doi.org/10.1172/JCI84424] [PMID: 28248199]
[http://dx.doi.org/10.3389/fnbeh.2018.00175] [PMID: 30323747]
[http://dx.doi.org/10.1186/s12929-020-00636-z] [PMID: 32264890]
[http://dx.doi.org/10.1101/cshperspect.a028035] [PMID: 28062563]
[http://dx.doi.org/10.1186/s12929-019-0524-y] [PMID: 31072403]
[http://dx.doi.org/10.1101/cshperspect.a006148] [PMID: 22553492]
[http://dx.doi.org/10.1016/j.ncl.2016.06.009] [PMID: 27720002]
[http://dx.doi.org/10.3233/JAD-161088] [PMID: 28059794]
[http://dx.doi.org/10.1073/pnas.1912954116] [PMID: 31871211]
[http://dx.doi.org/10.1038/aps.2017.28] [PMID: 28713158]
[http://dx.doi.org/10.1186/s13024-019-0333-5] [PMID: 31375134]
[http://dx.doi.org/10.1016/j.mad.2020.111319] [PMID: 32721406]
[http://dx.doi.org/10.1007/s10433-012-0234-8] [PMID: 28804426]
[http://dx.doi.org/10.1093/brain/awr038] [PMID: 21436112]
[http://dx.doi.org/10.1016/j.jalz.2011.03.005] [PMID: 21514250]
[http://dx.doi.org/10.1007/s11357-022-00591-7] [PMID: 35585301]
[http://dx.doi.org/10.1007/s40120-017-0069-5] [PMID: 28733959]
[http://dx.doi.org/10.3389/fnagi.2021.654978] [PMID: 34276336]
[http://dx.doi.org/10.1016/j.arr.2021.101425] [PMID: 34384901]
[http://dx.doi.org/10.1016/j.neurobiolaging.2015.07.015] [PMID: 26318290]
[http://dx.doi.org/10.3233/JAD-142919] [PMID: 25624420]
[http://dx.doi.org/10.1016/j.neurobiolaging.2019.05.023] [PMID: 31280115]
[http://dx.doi.org/10.1038/nm1784] [PMID: 18587408]
[http://dx.doi.org/10.1186/gb-2010-11-5-r56] [PMID: 20507594]
[http://dx.doi.org/10.1016/j.celrep.2014.04.050] [PMID: 24857657]
[PMID: 22996644]
[http://dx.doi.org/10.1007/s12017-011-8154-x] [PMID: 21898045]
[http://dx.doi.org/10.3233/JAD-2009-1051] [PMID: 19363274]
[http://dx.doi.org/10.1038/nbt.2158] [PMID: 22446693]
[http://dx.doi.org/10.18632/aging.102785] [PMID: 32035423]
[http://dx.doi.org/10.1371/journal.pone.0281784] [PMID: 36947499]
[http://dx.doi.org/10.1126/science.abp9556] [PMID: 37708272]
[http://dx.doi.org/10.1016/j.arr.2023.101878] [PMID: 36738893]
[http://dx.doi.org/10.1089/dna.2017.4012] [PMID: 29298096]
[http://dx.doi.org/10.15252/embj.201387576] [PMID: 25001178]
[http://dx.doi.org/10.1523/JNEUROSCI.5065-07.2008] [PMID: 18234899]
[http://dx.doi.org/10.3233/JAD-2010-091603] [PMID: 20413881]
[http://dx.doi.org/10.1038/mtna.2015.33] [PMID: 26440600]
[http://dx.doi.org/10.15252/emmm.201606520] [PMID: 27485122]
[http://dx.doi.org/10.1093/hmg/ddv377] [PMID: 26362250]
[http://dx.doi.org/10.1038/srep26697] [PMID: 27221467]
[http://dx.doi.org/10.1016/j.stem.2021.05.001]
[http://dx.doi.org/10.1016/j.arr.2021.101497] [PMID: 34710587]
[http://dx.doi.org/10.1038/s41593-023-01355-y] [PMID: 37291336]
[http://dx.doi.org/10.3892/mmr.2014.2484] [PMID: 25119742]
[http://dx.doi.org/10.1016/j.biopsych.2017.07.023] [PMID: 28965984]
[http://dx.doi.org/10.1016/j.neurobiolaging.2016.12.015] [PMID: 28089352]
[http://dx.doi.org/10.1016/j.neuroscience.2014.06.013] [PMID: 24950120]
[http://dx.doi.org/10.1002/jcb.26700] [PMID: 29369410]
[http://dx.doi.org/10.1038/nature11928] [PMID: 23446348]
[http://dx.doi.org/10.1016/j.molcel.2015.03.027] [PMID: 25921068]
[http://dx.doi.org/10.1080/15476286.2020.1783487] [PMID: 32618510]
[http://dx.doi.org/10.1038/s41593-019-0501-5] [PMID: 31591557]
[http://dx.doi.org/10.3389/fgene.2013.00307] [PMID: 24427167]
[http://dx.doi.org/10.1016/j.omtn.2019.10.030] [PMID: 31786335]
[http://dx.doi.org/10.1038/s41418-021-00865-1] [PMID: 34504314]
[http://dx.doi.org/10.1007/s12264-019-00361-0] [PMID: 30887246]
[http://dx.doi.org/10.1002/brb3.2048] [PMID: 33704916]
[http://dx.doi.org/10.1186/s40035-020-00216-z] [PMID: 32951610]
[http://dx.doi.org/10.3389/fgene.2023.1231486] [PMID: 37790702]
[http://dx.doi.org/10.3389/fcell.2021.647197] [PMID: 33777952]
[http://dx.doi.org/10.1093/nar/gkac1129] [PMID: 36533443]
[http://dx.doi.org/10.1016/j.biocel.2020.105747] [PMID: 32315771]
[http://dx.doi.org/10.1002/alz.12960] [PMID: 36795937]
[http://dx.doi.org/10.1021/bi201215r] [PMID: 22471593]
[http://dx.doi.org/10.1111/bpa.12133] [PMID: 24571648]
[http://dx.doi.org/10.1073/pnas.1310249110] [PMID: 24023061]
[http://dx.doi.org/10.1021/pr5003593] [PMID: 24902715]
[http://dx.doi.org/10.1080/01677063.2017.1395425] [PMID: 29098922]
[http://dx.doi.org/10.1016/j.neurobiolaging.2020.12.015] [PMID: 33450722]
[http://dx.doi.org/10.3233/JAD-220110] [PMID: 35527555]
[PMID: 23459401]
[http://dx.doi.org/10.59566/IJBS.2017.13048] [PMID: 28824341]
[http://dx.doi.org/10.1074/jbc.M110.170217] [PMID: 21245145]
[http://dx.doi.org/10.1126/sciadv.abc7031] [PMID: 33036977]
[http://dx.doi.org/10.1002/ana.10208] [PMID: 12112088]
[http://dx.doi.org/10.1002/ana.20144] [PMID: 15174031]
[http://dx.doi.org/10.3390/ijms241512498] [PMID: 37569871]
[http://dx.doi.org/10.1111/jcmm.15439] [PMID: 32521573]
[http://dx.doi.org/10.1101/gad.12.23.3715] [PMID: 9851978]
[http://dx.doi.org/10.2741/4789] [PMID: 31136989]
[PMID: 31838836]
[http://dx.doi.org/10.1016/j.neurobiolaging.2017.05.020] [PMID: 28654860]
[http://dx.doi.org/10.1039/C6MB00699J] [PMID: 28127595]
[http://dx.doi.org/10.4103/1673-5374.284990] [PMID: 32594043]
[PMID: 36453246]
[http://dx.doi.org/10.3389/fnmol.2021.685143] [PMID: 34421536]
[http://dx.doi.org/10.1007/978-3-030-05542-4_2] [PMID: 30747416]
[http://dx.doi.org/10.1186/s12883-017-1008-x] [PMID: 29316899]
[http://dx.doi.org/10.3892/mmr.2020.11118] [PMID: 32377715]
[http://dx.doi.org/10.1155/2020/2901589]
[http://dx.doi.org/10.3389/fnagi.2020.598606] [PMID: 33584243]
[http://dx.doi.org/10.2174/1567205016666190725130134] [PMID: 31345147]
[PMID: 35949493]
[http://dx.doi.org/10.1080/01616412.2023.2203616] [PMID: 37486018]
[http://dx.doi.org/10.5114/fn.2022.118961] [PMID: 36734383]
[http://dx.doi.org/10.3389/fnmol.2020.00160] [PMID: 32973449]
[http://dx.doi.org/10.3233/JAD-190583] [PMID: 31524168]
[http://dx.doi.org/10.3389/fnmol.2014.00002] [PMID: 24550773]
[http://dx.doi.org/10.1186/s13195-019-0501-4] [PMID: 31092279]
[http://dx.doi.org/10.1186/s40478-017-0414-z] [PMID: 28137310]
[http://dx.doi.org/10.2147/NDT.S290925] [PMID: 33542630]
[http://dx.doi.org/10.3233/JAD-170343] [PMID: 29036818]
[http://dx.doi.org/10.1155/2015/625659] [PMID: 26078483]
[http://dx.doi.org/10.1620/tjem.242.129] [PMID: 28626163]
[http://dx.doi.org/10.1038/s41598-022-19862-6] [PMID: 36114255]
[http://dx.doi.org/10.3892/etm.2022.11166] [PMID: 35222718]
[http://dx.doi.org/10.1002/alz.13055] [PMID: 37071449]
[http://dx.doi.org/10.1002/dad2.12251] [PMID: 35141392]
[http://dx.doi.org/10.1007/s12035-023-03446-0] [PMID: 37386272]
[http://dx.doi.org/10.1016/j.nbd.2021.105481] [PMID: 34411703]
[http://dx.doi.org/10.1038/s41398-019-0579-2] [PMID: 31591382]
[http://dx.doi.org/10.1016/j.nbd.2020.105058] [PMID: 32835860]
[http://dx.doi.org/10.1002/trc2.12179] [PMID: 34095440]
[http://dx.doi.org/10.1016/j.biopha.2021.111623] [PMID: 33915504]
[http://dx.doi.org/10.1186/s12929-019-0609-7] [PMID: 31906949]
[http://dx.doi.org/10.3390/pharmaceutics13091397] [PMID: 34575473]
[http://dx.doi.org/10.3389/fimmu.2022.908076] [PMID: 35720333]
[http://dx.doi.org/10.1186/s13024-021-00496-7] [PMID: 34742333]
[http://dx.doi.org/10.1016/j.biopha.2022.112681] [PMID: 35177290]
[http://dx.doi.org/10.3390/genes9040174] [PMID: 29561798]
[http://dx.doi.org/10.3390/ijms20163979] [PMID: 31443326]
[http://dx.doi.org/10.1042/BSR20180051] [PMID: 29961672]
[http://dx.doi.org/10.1016/j.jns.2020.116793] [PMID: 32251872]
[http://dx.doi.org/10.1016/j.omtn.2020.01.010] [PMID: 32069773]
[PMID: 25973041]
[http://dx.doi.org/10.1371/journal.pone.0196929] [PMID: 29738527]
[http://dx.doi.org/10.1038/s41380-019-0610-2] [PMID: 31942037]
[http://dx.doi.org/10.1080/09168451.2020.1797469] [PMID: 32713252]
[http://dx.doi.org/10.1007/s12038-017-9698-1] [PMID: 29358553]
[http://dx.doi.org/10.1038/srep30953] [PMID: 27484949]
[http://dx.doi.org/10.1016/j.neuro.2016.07.004] [PMID: 27397902]
[http://dx.doi.org/10.18632/oncotarget.15149] [PMID: 28186985]
[http://dx.doi.org/10.1002/jcp.28988] [PMID: 31385301]
[http://dx.doi.org/10.12659/MSM.908765] [PMID: 30102687]
[http://dx.doi.org/10.1016/j.ejphar.2018.11.004] [PMID: 30412727]
[http://dx.doi.org/10.1016/j.cbi.2019.108908] [PMID: 31778666]
[http://dx.doi.org/10.1111/acel.13125] [PMID: 32092796]
[http://dx.doi.org/10.1016/j.expneurol.2019.113128] [PMID: 31759899]
[http://dx.doi.org/10.1016/j.brainres.2015.07.022] [PMID: 26212654]
[http://dx.doi.org/10.1007/s12011-021-03073-7] [PMID: 35059981]
[http://dx.doi.org/10.1016/j.neuropharm.2016.04.046] [PMID: 27143098]
[http://dx.doi.org/10.1016/j.lfs.2019.04.004] [PMID: 30951743]
[http://dx.doi.org/10.1007/s12031-016-0793-9] [PMID: 27394443]
[http://dx.doi.org/10.1016/j.mcn.2017.11.012] [PMID: 29174617]
[http://dx.doi.org/10.3233/JPD-171203] [PMID: 29036837]
[http://dx.doi.org/10.1002/jcb.29108] [PMID: 31190362]
[http://dx.doi.org/10.1080/09168451.2018.1562874] [PMID: 30652945]
[http://dx.doi.org/10.1016/j.biopha.2018.08.155] [PMID: 30248538]
[http://dx.doi.org/10.1007/s12035-018-1299-y] [PMID: 30143969]
[http://dx.doi.org/10.1080/01616412.2018.1548747] [PMID: 31014193]
[http://dx.doi.org/10.3892/etm.2018.6359] [PMID: 30186443]
[http://dx.doi.org/10.1016/j.cell.2012.02.057] [PMID: 22541438]
[http://dx.doi.org/10.1080/15384101.2019.1629773] [PMID: 31373242]
[http://dx.doi.org/10.1016/j.brainres.2021.147622] [PMID: 34403662]
[http://dx.doi.org/10.3389/fnmol.2017.00227] [PMID: 28769761]
[http://dx.doi.org/10.1016/j.lfs.2020.117637] [PMID: 32251633]
[http://dx.doi.org/10.1007/s11356-021-17478-3] [PMID: 35060046]
[http://dx.doi.org/10.1007/s11011-022-00912-x] [PMID: 35076819]
[http://dx.doi.org/10.1007/s11064-022-03563-7] [PMID: 35229272]
[http://dx.doi.org/10.21037/atm-20-3749] [PMID: 32647679]
[http://dx.doi.org/10.1038/s41573-021-00219-z] [PMID: 34145432]
[http://dx.doi.org/10.3349/ymj.2019.60.7.640] [PMID: 31250578]
[http://dx.doi.org/10.1002/jcb.27541] [PMID: 30203508]
[http://dx.doi.org/10.1016/j.yexmp.2020.104545] [PMID: 32976819]
[PMID: 34540002]
[http://dx.doi.org/10.3892/mmr.2020.11203] [PMID: 32626959]
[http://dx.doi.org/10.1016/j.exger.2020.111180] [PMID: 33279663]
[http://dx.doi.org/10.4061/2011/929042] [PMID: 21785702]
[http://dx.doi.org/10.3389/fneur.2021.653267] [PMID: 33967943]
[http://dx.doi.org/10.1016/j.bbamcr.2012.05.001] [PMID: 22580042]
[http://dx.doi.org/10.3389/fneur.2020.00462] [PMID: 32670176]
[http://dx.doi.org/10.1016/j.jns.2013.10.002] [PMID: 24139697]
[http://dx.doi.org/10.1080/13813455.2020.1734842] [PMID: 32141790]
[http://dx.doi.org/10.1038/s41380-020-0824-3] [PMID: 32632205]
[http://dx.doi.org/10.3390/cells10010113] [PMID: 33435363]
[PMID: 32934666]
[http://dx.doi.org/10.18632/oncotarget.21177] [PMID: 29207665]
[http://dx.doi.org/10.3390/ijms22073653] [PMID: 33915734]
[http://dx.doi.org/10.18632/oncotarget.15109] [PMID: 28179587]
[http://dx.doi.org/10.1371/journal.pone.0200602] [PMID: 30011310]
[http://dx.doi.org/10.1007/s12035-015-9156-8] [PMID: 25895659]
[http://dx.doi.org/10.3233/JAD-180539] [PMID: 30689565]
[http://dx.doi.org/10.1371/journal.pone.0126423] [PMID: 25992776]
[http://dx.doi.org/10.1007/s12035-016-0088-8] [PMID: 27631879]
[http://dx.doi.org/10.3109/1354750X.2013.814073] [PMID: 23822153]
[http://dx.doi.org/10.1016/j.neurobiolaging.2017.11.007] [PMID: 29253717]