Abstract
Neurodevelopmental Disorders (NDDs) are abnormalities linked to neuronal structure and irregularities associated with the proliferation of cells, transportation, and differentiation. NDD also involves synaptic circuitry and neural network alterations known as synaptopathy. Microtubules (MTs) and MTs-associated proteins help to maintain neuronal health as well as their development. The microtubular dynamic structure plays a crucial role in the division of cells and forms mitotic spindles, thus take part in initiating stages of differentiation and polarization for various types of cells. The MTs also take part in cellular death, but MT-based cellular degenerations are not yet well excavated. In the last few years, studies have provided the protagonist activity of MTs in neuronal degeneration. In this review, we largely engrossed our discussion on the change of MT cytoskeleton structure, describing their organization, dynamics, transportation, and their failure causing NDDs. At the end of this review, we are targeting the therapeutic neuroprotective strategies on clinical priority and also try to discuss the clues for the development of new MT-based therapy as a new pharmacological intervention. This will be a new potential site to block not only neurodegeneration but also promotes the regeneration of neurons.
Keywords: Microtubule, MT-based transport, neurodevelopmental disorders, tubulin based therapy, oxidative stresses, inflammatory responses.
Graphical Abstract
[http://dx.doi.org/10.1016/j.tins.2010.03.006] [PMID: 20434225]
[http://dx.doi.org/10.1016/j.gde.2011.01.003] [PMID: 21292473]
[http://dx.doi.org/10.1038/nrn3380] [PMID: 23361386]
[http://dx.doi.org/10.1016/j.neuron.2014.09.027] [PMID: 25374358]
[http://dx.doi.org/10.1016/j.ejmech.2017.11.062] [PMID: 29223097]
[http://dx.doi.org/10.1016/j.neuron.2015.05.046] [PMID: 26247859]
[http://dx.doi.org/10.1016/j.cub.2009.12.052] [PMID: 20137950]
[http://dx.doi.org/10.1093/brain/awv234] [PMID: 26297556]
[http://dx.doi.org/10.1016/j.tins.2014.08.004] [PMID: 25223701]
[http://dx.doi.org/10.1083/jcb.201406055] [PMID: 25135932]
[http://dx.doi.org/10.1242/jcs.107.6.1529] [PMID: 7962195]
[http://dx.doi.org/10.1016/j.cell.2014.03.061] [PMID: 24906155]
[http://dx.doi.org/10.1242/jcs.101139] [PMID: 22595526]
[http://dx.doi.org/10.1016/j.cub.2006.09.014] [PMID: 17084703]
[http://dx.doi.org/10.1242/jcs.026492] [PMID: 18334549]
[http://dx.doi.org/10.1016/j.cell.2010.10.014] [PMID: 21074048]
[http://dx.doi.org/10.1083/jcb.201211017] [PMID: 23358242]
[http://dx.doi.org/10.1074/jbc.M114.622753] [PMID: 25911101]
[http://dx.doi.org/10.1371/journal.pone.0005405] [PMID: 19404406]
[http://dx.doi.org/10.1016/S0962-8924(97)01168-9] [PMID: 17709011]
[http://dx.doi.org/10.1074/jbc.C116.731133] [PMID: 27129203]
[http://dx.doi.org/10.1038/ncb2920] [PMID: 24633327]
[http://dx.doi.org/10.1038/nmat4396] [PMID: 26343914]
[http://dx.doi.org/10.1016/j.cell.2011.10.037] [PMID: 22118464]
[http://dx.doi.org/10.1002/bies.201200131] [PMID: 23532586]
[http://dx.doi.org/10.1016/j.cub.2013.05.059] [PMID: 23831290]
[http://dx.doi.org/10.1038/35004008] [PMID: 10707083]
[http://dx.doi.org/10.1083/jcb.201106120] [PMID: 22331844]
[http://dx.doi.org/10.1096/fj.09-129585] [PMID: 19451279]
[http://dx.doi.org/10.1091/mbc.e09-04-0304] [PMID: 19812246]
[http://dx.doi.org/10.1016/j.neuron.2010.09.039] [PMID: 21092854]
[http://dx.doi.org/10.1016/j.celrep.2015.02.061] [PMID: 25818289]
[http://dx.doi.org/10.1083/jcb.152.5.959] [PMID: 11238452]
[http://dx.doi.org/10.1038/nature743] [PMID: 11986669]
[http://dx.doi.org/10.1016/j.pharmthera.2011.03.004] [PMID: 21420428]
[http://dx.doi.org/10.1146/annurev.cellbio.20.012103.094623] [PMID: 15473859]
[http://dx.doi.org/10.1038/nrm3248] [PMID: 22146746]
[http://dx.doi.org/10.1091/mbc.e03-07-0504] [PMID: 14565972]
[http://dx.doi.org/10.1371/journal.pone.0017087] [PMID: 21359212]
[http://dx.doi.org/10.1242/jcs.00727] [PMID: 14576357]
[http://dx.doi.org/10.1073/pnas.0611471104] [PMID: 17360524]
[http://dx.doi.org/10.1093/emboj/21.3.281] [PMID: 11823421]
[http://dx.doi.org/10.1016/S0014-5793(97)00240-8] [PMID: 9109420]
[http://dx.doi.org/10.1128/MCB.22.5.1352-1359.2002] [PMID: 11839802]
[http://dx.doi.org/10.1038/sj.emboj.7600237] [PMID: 15152189]
[http://dx.doi.org/10.1242/jcs.00785] [PMID: 14762105]
[http://dx.doi.org/10.1016/j.molbrainres.2005.08.009] [PMID: 16246456]
[http://dx.doi.org/10.1126/science.1152993] [PMID: 18202255]
[http://dx.doi.org/10.1074/jbc.M111.292987] [PMID: 22039058]
[http://dx.doi.org/10.1523/JNEUROSCI.5242-07.2008] [PMID: 18272688]
[http://dx.doi.org/10.1016/j.cell.2011.01.021] [PMID: 21335237]
[http://dx.doi.org/10.1038/nrneurol.2015.197] [PMID: 26503923]
[http://dx.doi.org/10.1242/jcs.00967] [PMID: 14996933]
[http://dx.doi.org/10.1016/j.neuron.2004.11.008] [PMID: 15541303]
[http://dx.doi.org/10.1038/nrn1868] [PMID: 16495942]
[http://dx.doi.org/10.1074/jbc.M113.507913] [PMID: 24275654]
[http://dx.doi.org/10.1111/j.1471-4159.2009.06235.x] [PMID: 19545277]
[http://dx.doi.org/10.1371/journal.pone.0037467] [PMID: 22666358]
[http://dx.doi.org/10.1038/ncomms6245] [PMID: 25316291]
[http://dx.doi.org/10.1016/j.stemcr.2015.11.004] [PMID: 26651604]
[http://dx.doi.org/10.1074/jbc.M500843200] [PMID: 15737990]
[http://dx.doi.org/10.1074/jbc.M806245200] [PMID: 19074146]
[http://dx.doi.org/10.1002/stem.1854] [PMID: 25332110]
[http://dx.doi.org/10.1074/jbc.M102981200] [PMID: 11698390]
[http://dx.doi.org/10.3389/neuro.24.005.2009] [PMID: 20552056]
[http://dx.doi.org/10.2353/ajpath.2009.080503] [PMID: 19286568]
[http://dx.doi.org/10.3233/JAD-2004-6412] [PMID: 15345814]
[http://dx.doi.org/10.1016/j.bbrc.2007.02.163] [PMID: 17374364]
[http://dx.doi.org/10.1038/srep33289] [PMID: 27628239]
[http://dx.doi.org/10.1016/j.cell.2011.10.018] [PMID: 22078885]
[http://dx.doi.org/10.1038/ng.293] [PMID: 19136952]
[http://dx.doi.org/10.1093/brain/aws133] [PMID: 22719003]
[http://dx.doi.org/10.1016/j.neuron.2006.09.016] [PMID: 17015223]
[http://dx.doi.org/10.1097/WCO.0b013e32835ef373] [PMID: 23449172]
[http://dx.doi.org/10.1093/brain/awh681] [PMID: 16291806]
[http://dx.doi.org/10.1177/08830738030180111101] [PMID: 14696906]
[http://dx.doi.org/10.2174/156720510793611592] [PMID: 20678074]
[http://dx.doi.org/10.1002/j.1460-2075.1995.tb07116.x] [PMID: 7729409]
[http://dx.doi.org/10.1007/s12035-010-8141-5] [PMID: 20461558]
[http://dx.doi.org/10.1074/jbc.M000389200] [PMID: 10747907]
[http://dx.doi.org/10.1016/j.braindev.2014.08.010] [PMID: 25451314]
[http://dx.doi.org/10.1126/science.1105681] [PMID: 15731448]
[http://dx.doi.org/10.1016/j.neuron.2006.05.022] [PMID: 16815330]
[http://dx.doi.org/10.1523/JNEUROSCI.4272-06.2007] [PMID: 17596450]
[http://dx.doi.org/10.1523/JNEUROSCI.0797-04.2004] [PMID: 15140937]
[http://dx.doi.org/10.1038/414643a] [PMID: 11740561]
[http://dx.doi.org/10.1523/JNEUROSCI.3089-04.2005] [PMID: 15745965]
[http://dx.doi.org/10.1111/j.1600-0854.2006.00434.x] [PMID: 16734669]
[http://dx.doi.org/10.1523/JNEUROSCI.23-26-08967.2003] [PMID: 14523099]
[http://dx.doi.org/10.1073/pnas.0901229106] [PMID: 19321417]
[http://dx.doi.org/10.1093/emboj/cdf503] [PMID: 12234929]
[http://dx.doi.org/10.1002/jnr.21154] [PMID: 17265463]
[http://dx.doi.org/10.1523/JNEUROSCI.0560-11.2011] [PMID: 21734277]
[http://dx.doi.org/10.1006/nbdi.1999.0279] [PMID: 10783293]
[http://dx.doi.org/10.1038/45159] [PMID: 10604467]
[PMID: 9150168]
[http://dx.doi.org/10.1523/JNEUROSCI.21-21-08473.2001] [PMID: 11606636]
[http://dx.doi.org/10.1016/S0896-6273(03)00569-5] [PMID: 14527432]
[http://dx.doi.org/10.1016/S0896-6273(03)00594-4] [PMID: 14527431]
[http://dx.doi.org/10.1128/MCB.24.18.8195-8209.2004] [PMID: 15340079]
[http://dx.doi.org/10.1074/jbc.M509806200] [PMID: 16339760]
[http://dx.doi.org/10.1073/pnas.0610628104] [PMID: 17548833]
[http://dx.doi.org/10.1091/mbc.e10-03-0233] [PMID: 21169558]
[http://dx.doi.org/10.1016/j.cell.2004.06.018] [PMID: 15242649]
[http://dx.doi.org/10.1016/j.neuron.2009.12.007] [PMID: 20152113]
[http://dx.doi.org/10.1038/emboj.2008.133] [PMID: 18615096]
[http://dx.doi.org/10.1126/science.1175371] [PMID: 19608861]
[http://dx.doi.org/10.1523/JNEUROSCI.0037-07.2007] [PMID: 17392473]
[http://dx.doi.org/10.1371/journal.pone.0020696] [PMID: 21677773]
[http://dx.doi.org/10.1074/jbc.M508786200] [PMID: 16192271]
[http://dx.doi.org/10.1038/nn.2346] [PMID: 19525941]
[http://dx.doi.org/10.1083/jcb.150.1.165] [PMID: 10893265]
[http://dx.doi.org/10.1242/jcs.113.3.401] [PMID: 10639328]
[http://dx.doi.org/10.1038/nn1717] [PMID: 16751763]
[http://dx.doi.org/10.1093/hmg/8.2.157] [PMID: 9931323]
[http://dx.doi.org/10.1074/jbc.M408139200] [PMID: 15322088]
[http://dx.doi.org/10.1002/neu.10270] [PMID: 14598376]
[http://dx.doi.org/10.1111/j.1471-4159.2006.03932.x] [PMID: 16787413]
[http://dx.doi.org/10.1093/brain/awr159] [PMID: 21752789]
[http://dx.doi.org/10.1016/j.brainres.2009.09.105] [PMID: 19815002]
[http://dx.doi.org/10.1016/S0896-6273(00)80272-X] [PMID: 9052802]
[http://dx.doi.org/10.1038/4553] [PMID: 10195180]
[http://dx.doi.org/10.1016/S1044-7431(03)00022-8] [PMID: 12812752]
[http://dx.doi.org/10.1016/S0896-6273(01)00268-9] [PMID: 11343650]
[http://dx.doi.org/10.1038/nn.2660] [PMID: 20953194]
[http://dx.doi.org/10.1093/hmg/ddm226] [PMID: 17725983]
[http://dx.doi.org/10.1073/pnas.1006869107] [PMID: 21059924]
[http://dx.doi.org/10.1371/journal.pone.0022031] [PMID: 21779368]
[http://dx.doi.org/10.1073/pnas.1200658109] [PMID: 22371592]
[http://dx.doi.org/10.1016/S0896-6273(02)00696-7] [PMID: 12062019]
[http://dx.doi.org/10.1038/ng1123] [PMID: 12627231]
[http://dx.doi.org/10.1523/JNEUROSCI.4231-07.2008] [PMID: 18305234]
[http://dx.doi.org/10.1093/hmg/ddn092] [PMID: 18364389]
[http://dx.doi.org/10.1093/hmg/ddn182] [PMID: 18579581]
[http://dx.doi.org/10.1093/hmg/ddg184] [PMID: 12837691]
[http://dx.doi.org/10.1093/hmg/ddn171] [PMID: 18558633]
[http://dx.doi.org/10.1523/JNEUROSCI.2661-07.2007] [PMID: 17804640]
[http://dx.doi.org/10.4306/pi.2015.12.1.37] [PMID: 25670944]
[http://dx.doi.org/10.1016/j.dcn.2010.07.002] [PMID: 21151713]
[http://dx.doi.org/10.1016/j.nicl.2013.01.010] [PMID: 24179785]
[http://dx.doi.org/10.1038/ng.2899] [PMID: 24531329]
[http://dx.doi.org/10.1016/j.nbd.2013.04.012] [PMID: 23631872]
[http://dx.doi.org/10.1007/s12017-015-8357-7] [PMID: 25989848]
[http://dx.doi.org/10.1128/MCB.17.3.1201] [PMID: 9032247]
[http://dx.doi.org/10.1016/j.neuron.2015.10.031] [PMID: 26627310]
[http://dx.doi.org/10.1074/jbc.M401915200] [PMID: 15277531]
[http://dx.doi.org/10.1038/ncomms8246] [PMID: 26037503]
[http://dx.doi.org/10.1016/j.neuroscience.2015.11.003] [PMID: 26562433]
[http://dx.doi.org/10.1016/j.psychres.2016.08.024] [PMID: 27541346]
[http://dx.doi.org/10.1111/j.1471-4159.2011.07615.x] [PMID: 22146001]
[http://dx.doi.org/10.1002/ajmg.a.35621] [PMID: 22965935]
[http://dx.doi.org/10.1371/journal.pone.0053123] [PMID: 23300879]
[http://dx.doi.org/10.3390/brainsci7050054] [PMID: 28505103]
[http://dx.doi.org/10.1093/emboj/cdg413] [PMID: 12912917]
[http://dx.doi.org/10.1093/hmg/ddx023] [PMID: 28158563]
[http://dx.doi.org/10.1016/j.tibs.2009.03.008] [PMID: 19559622]
[http://dx.doi.org/10.1093/hmg/ddn154] [PMID: 18492799]
[http://dx.doi.org/10.1038/nature11011] [PMID: 22495311]
[http://dx.doi.org/10.1038/srep25611] [PMID: 27161796]
[http://dx.doi.org/10.1038/nn.2741] [PMID: 21346746]
[http://dx.doi.org/10.1038/nrm3227] [PMID: 22086369]
[http://dx.doi.org/10.1002/cm.21300] [PMID: 27112918]
[http://dx.doi.org/10.1242/jcs.137604] [PMID: 24284070]
[http://dx.doi.org/10.1016/j.tcb.2014.10.004] [PMID: 25468068]
[http://dx.doi.org/10.1038/nrn4002] [PMID: 26289573]
[http://dx.doi.org/10.1074/jbc.M113.457267] [PMID: 23831686]
[http://dx.doi.org/10.1016/j.neuropharm.2010.12.027] [PMID: 21195721]
[http://dx.doi.org/10.1016/j.euroneuro.2010.06.004] [PMID: 20598862]
[http://dx.doi.org/10.1038/sj.mp.4000580] [PMID: 10673773]
[http://dx.doi.org/10.1007/s00726-015-2062-6] [PMID: 26269195]
[http://dx.doi.org/10.1016/j.nicl.2013.05.006] [PMID: 24179822]
[http://dx.doi.org/10.1016/j.ajpath.2011.10.037] [PMID: 22182700]
[http://dx.doi.org/10.4161/cc.29104] [PMID: 24806449]
[http://dx.doi.org/10.1097/NEN.0b013e31827733c8] [PMID: 23147510]
[http://dx.doi.org/10.1016/j.pharmthera.2018.09.010] [PMID: 30268771]
[http://dx.doi.org/10.1016/j.braindev.2015.12.005] [PMID: 26743950]
[PMID: 26730336]
[http://dx.doi.org/10.1074/jbc.M106628200] [PMID: 11694528]
[http://dx.doi.org/10.1002/path.1650]
[PMID: 12803483]
[http://dx.doi.org/10.3109/00207454.2011.558224] [PMID: 21370991]
[http://dx.doi.org/10.1038/cr.2012.40] [PMID: 22430151]
[http://dx.doi.org/10.1242/dev.139964] [PMID: 28126842]
[http://dx.doi.org/10.1007/s12035-015-9431-8] [PMID: 26377107]
[http://dx.doi.org/10.1080/02841860903104145] [PMID: 19639468]
[http://dx.doi.org/10.1038/ejhg.2014.13] [PMID: 24569606]
[http://dx.doi.org/10.1016/j.cub.2016.01.048] [PMID: 26948876]
[http://dx.doi.org/10.1002/acn3.198] [PMID: 26125038]
[http://dx.doi.org/10.1016/j.ajhg.2015.08.003] [PMID: 26340335]
[http://dx.doi.org/10.1038/mp.2017.54] [PMID: 28373692]
[http://dx.doi.org/10.1016/j.celrep.2015.12.035] [PMID: 26748699]
[http://dx.doi.org/10.1523/JNEUROSCI.3059-10.2010] [PMID: 20943926]
[http://dx.doi.org/10.1016/j.biopsych.2006.03.048] [PMID: 16806091]
[http://dx.doi.org/10.1007/s12031-007-9013-y] [PMID: 18286385]
[http://dx.doi.org/10.1186/2193-1801-4-S1-L37] [PMID: 27386198]
[http://dx.doi.org/10.1038/mp.2013.174] [PMID: 24365867]
[http://dx.doi.org/10.1038/mp.2014.97] [PMID: 25178163]
[http://dx.doi.org/10.1038/mp.2013.32] [PMID: 23587881]
[http://dx.doi.org/10.1038/srep16300] [PMID: 26553741]
[http://dx.doi.org/10.4161/15548627.2014.984274] [PMID: 25484074]
[http://dx.doi.org/10.1097/HRP.0000000000000030] [PMID: 24614763]
[http://dx.doi.org/10.1111/j.1742-1241.2006.01191.x] [PMID: 17298593]
[http://dx.doi.org/10.1093/ijnp/pyv119] [PMID: 26476437]
[http://dx.doi.org/10.1021/acschemneuro.6b00384] [PMID: 28095679]
[http://dx.doi.org/10.1021/jm060717i] [PMID: 17228873]
[http://dx.doi.org/10.1021/jm5005623] [PMID: 24992153]