摘要
阿尔茨海默氏病(AD)是一种慢性进行性神经退行性疾病,全世界有4600万人受到影响。它的特点是认知能力下降,包括记忆和思维能力。 AD患者还患有痴呆的行为和心理症状,其中抑郁症最普遍。目前可用的药物可提供适度的症状缓解,并且不能减轻病理特征(老年斑和神经原纤维缠结)和神经炎症,这两者都是AD的组成部分。研究表明,AD是一种表现在大脑中的糖尿病。尽管AD和糖尿病目前被分类为单独的疾病实体,但是它们具有共同的病理生理机制,其中之一是参与炎症以及调节代谢,再生和神经过程的细胞因子水平升高。这篇综述的目的是更新有关抗糖尿病药的发现和开发的最新报告,这些药物是用于对症和疾病缓解性治疗的有前途的药物。我们收集了体外和体内研究的结果,最近的临床试验报告表明抗糖尿病药在AD记忆增强疗法中的实用性。还介绍了它们对慢性神经发炎,病理学特征和认知缺陷共同引起的神经精神症状的有益作用。抗糖尿病药是指AD的糖尿病和炎症假设,并为寻找一种有效的药物来对该疾病进行综合治疗提供了希望。
关键词: 阿尔茨海默氏病,BPSD,认知障碍,神经退行性疾病,神经炎症,III型糖尿病,抗糖尿病药,抗炎活性。
[http://dx.doi.org/10.1016/j.ncl.2007.03.008] [PMID: 17659182]
[http://dx.doi.org/10.3389/fneur.2012.00073] [PMID: 22586419]
[http://dx.doi.org/10.3389/fphar.2017.00739] [PMID: 29123479]
[http://dx.doi.org/10.1371/journal.pone.0210958] [PMID: 30682120]
[http://dx.doi.org/10.3892/mmr.2019.10374 ] [PMID: 31257471]
[http://dx.doi.org/10.1007/s00210-014-0966-4] [PMID: 24599316]
[http://dx.doi.org/10.1136/bmj.e2986] [PMID: 22550350]
[http://dx.doi.org/10.3233/JAD-130395] [PMID: 23635410]
[http://dx.doi.org/10.1186/s12974-018-1313-3] [PMID: 30249283]
[http://dx.doi.org/10.1016/S1474-4422(15)70016-5] [PMID: 25792098]
[PMID: 20030463]
[http://dx.doi.org/10.2174/1568026617666170103163403] [PMID: 28049395]
[http://dx.doi.org/10.1016/j.bbadis.2016.08.018] [PMID: 27567931]
[http://dx.doi.org/10.3233/JAD-2005-8304] [PMID: 16340083]
[http://dx.doi.org/10.1111/j.1651-2227.1994.tb13300.x] [PMID: 7949626]
[http://dx.doi.org/10.2174/1871530319666190311141855] [PMID: 30854980]
[http://dx.doi.org/10.1007/978-981-13-3540-2_8] [PMID: 31062329]
[http://dx.doi.org/10.1038/nrneurol.2017.185] [PMID: 29377010]
[http://dx.doi.org/10.1186/s12979-019-0147-x] [PMID: 30984280]
[http://dx.doi.org/10.1155/2019/5953685] [PMID: 31214280]
[http://dx.doi.org/10.1007/s00394-016-1212-2] [PMID: 27084094]
[http://dx.doi.org/10.1016/j.neulet.2017.06.041] [PMID: 28652187]
[http://dx.doi.org/10.1002/ana.25570] [PMID: 31376172]
[http://dx.doi.org/10.4103/0366-6999.151082] [PMID: 25673447]
[http://dx.doi.org/10.1001/jama.292.18.2237] [PMID: 15536110]
[http://dx.doi.org/10.1016/j.neuint.2013.06.018] [PMID: 23876631]
[http://dx.doi.org/10.1177/2040622315608646] [PMID: 26568812]
[http://dx.doi.org/10.1093/gerona/glw065] [PMID: 27069097]
[http://dx.doi.org/10.1186/s12974-015-0282-z] [PMID: 25889938]
[http://dx.doi.org/10.1016/j.bbr.2008.09.008] [PMID: 18840474]
[http://dx.doi.org/10.1016/j.brainresbull.2018.09.017] [PMID: 30278200]
[http://dx.doi.org/10.2174/0929867326666190620095623] [PMID: 31250747]
[http://dx.doi.org/10.2174/0929867324666170529122802] [PMID: 28554324]
[http://dx.doi.org/10.1155/2014/674164] [PMID: 25018588]
[http://dx.doi.org/10.1073/pnas.051634698] [PMID: 11248117]
[http://dx.doi.org/10.1038/ncomms9543] [PMID: 26503322]
[http://dx.doi.org/10.1016/j.physbeh.2019.112640] [PMID: 31377312]
[http://dx.doi.org/10.1016/j.nbd.2019.104541] [PMID: 31349033]
[http://dx.doi.org/10.1016/j.jalz.2013.12.004] [PMID: 24529521]
[http://dx.doi.org/10.2147/DDDT.S141675] [PMID: 28860713]
[http://dx.doi.org/10.2174/1871530315666150316124019] [PMID: 25772174]
[http://dx.doi.org/10.1016/S1734-1140(10)70357-1] [PMID: 21098880]
[http://dx.doi.org/10.1016/j.brainres.2016.05.013] [PMID: 27174003]
[http://dx.doi.org/10.1016/j.expneurol.2018.09.008] [PMID: 30219731]
[http://dx.doi.org/10.1016/j.bbi.2017.12.009] [PMID: 29253574]
[http://dx.doi.org/10.22038/IJBMS.2017.24331.6071 ] [PMID: 29372032]
[http://dx.doi.org/10.5455/njppp.2015.5.1208201564]
[http://dx.doi.org/10.1016/j.pharep.2019.04.015] [PMID: 31382167]
[http://dx.doi.org/10.3233/JAD-181240] [PMID: 30958364]
[http://dx.doi.org/10.1096/fj.201802718R] [PMID: 30894020]
[http://dx.doi.org/10.1111/bph.14519] [PMID: 30318707]
[http://dx.doi.org/10.1111/1440-1681.12265] [PMID: 24862430]
[http://dx.doi.org/10.1007/s00210-018-1466-8] [PMID: 29379991]
[http://dx.doi.org/10.1016/j.euroneuro.2017.12.082]
[http://dx.doi.org/10.1016/j.brainres.2019.05.023] [PMID: 31121159]
[http://dx.doi.org/10.14336/AD.2017.1202] [PMID: 30705766]
[http://dx.doi.org/10.3389/fnagi.2018.00227] [PMID: 30100873]
[http://dx.doi.org/10.1089/cap.2017.0072] [PMID: 29620914]
[http://dx.doi.org/10.1016/j.pnpbp.2017.06.002]
[http://dx.doi.org/10.3390/molecules24142545] [PMID: 31336903]
[http://dx.doi.org/10.2174/1381612825666190716094852] [PMID: 31333088]
[http://dx.doi.org/10.2174/1570159X16666180828100002] [PMID: 30152284]
[http://dx.doi.org/10.1038/npp.2010.32] [PMID: 20336061]
[http://dx.doi.org/10.1016/j.nbd.2010.07.005] [PMID: 20655383]
[http://dx.doi.org/10.1111/j.2042-7158.2011.01432.x] [PMID: 22420664]
[http://dx.doi.org/10.1111/j.1472-8206.2009.00708.x] [PMID: 19656209]
[http://dx.doi.org/10.1016/j.neulet.2017.04.052] [PMID: 28458023]
[http://dx.doi.org/10.1016/j.neulet.2014.06.010] [PMID: 24933538]
[http://dx.doi.org/10.1186/s13098-019-0432-z] [PMID: 31073335]
[http://dx.doi.org/10.1155/2019/7915730] [PMID: 31217747]
[http://dx.doi.org/10.1155/2019/6386729] [PMID: 31015796]
[http://dx.doi.org/10.1038/s41598-018-38336-2] [PMID: 30765769]
[http://dx.doi.org/10.1007/s10753-018-0940-2] [PMID: 30488141]
[http://dx.doi.org/10.1111/j.1471-4159.2006.03758.x] [PMID: 16539667]
[http://dx.doi.org/10.1179/016164110X12556180206112] [PMID: 20350367]
[http://dx.doi.org/10.3892/mmr.2015.4292] [PMID: 26351751]
[http://dx.doi.org/10.1089/neu.2015.4361] [PMID: 27142118]
[http://dx.doi.org/10.1016/j.bbr.2012.03.006] [PMID: 22440233]
[http://dx.doi.org/10.1007/s00213-012-2722-0] [PMID: 22547332]
[http://dx.doi.org/10.1002/ana.24439] [PMID: 25974006]
[http://dx.doi.org/10.1016/j.jdiacomp.2017.01.006] [PMID: 28254448]
[http://dx.doi.org/10.1007/s00125-017-4499-5] [PMID: 29138876]
[http://dx.doi.org/10.1016/j.trci.2019.05.004] [PMID: 31304231]
[http://dx.doi.org/10.1001/archneurol.2010.229] [PMID: 20837824]
[http://dx.doi.org/10.1159/000318845] [PMID: 20733306]
[http://dx.doi.org/10.1056/NEJMp1309610] [PMID: 23992603]
[http://dx.doi.org/10.1016/j.ejps.2019.01.008] [PMID: 30639402]
[http://dx.doi.org/10.15171/apb.2019.032] [PMID: 31380254]
[http://dx.doi.org/10.1155/2007/39654] [PMID: 18317516]
[http://dx.doi.org/10.4103/1673-5374.165313] [PMID: 26604898]
[http://dx.doi.org/10.1016/j.apsb.2017.05.005] [PMID: 28752027]
[http://dx.doi.org/10.1055/s-2007-979837] [PMID: 8911983]
[http://dx.doi.org/10.4093/dmj.2011.35.4.340] [PMID: 21977453]
[http://dx.doi.org/10.1016/j.ejphar.2010.05.030] [PMID: 20639139]
[http://dx.doi.org/10.1007/s11064-016-1859-3] [PMID: 26886763]
[http://dx.doi.org/10.1016/j.neulet.2013.10.052]
[http://dx.doi.org/10.1016/j.atherosclerosis.2012.11.016] [PMID: 23218803]
[http://dx.doi.org/10.1016/j.jphs.2017.09.032] [PMID: 29056256]
[http://dx.doi.org/10.1038/s41598-017-18785-x] [PMID: 29339732]
[http://dx.doi.org/10.1038/srep03363] [PMID: 24285369]
[http://dx.doi.org/10.1111/fcp.12434] [PMID: 30451327]
[http://dx.doi.org/10.1016/j.brainresbull.2018.01.001] [PMID: 29307659]
[http://dx.doi.org/10.3233/JAD-2011-101524] [PMID: 21297276]
[http://dx.doi.org/10.1038/jcbfm.2012.166] [PMID: 23149556]
[http://dx.doi.org/10.1161/STROKEAHA.108.522409] [PMID: 19023097]
[http://dx.doi.org/10.1016/j.brainresbull.2018.06.006] [PMID: 29933037]
[http://dx.doi.org/10.1016/j.neurobiolaging.2017.12.009] [PMID: 29331730]
[http://dx.doi.org/10.1177/2042018814559725] [PMID: 25678953]
[http://dx.doi.org/10.1186/1471-2202-13-33] [PMID: 22443187]
[http://dx.doi.org/10.1038/sj.ijo.0802206] [PMID: 12629557]
[http://dx.doi.org/10.1111/fcp.12192] [PMID: 26935863]
[http://dx.doi.org/10.12659/MSMBR.891168] [PMID: 25076419]
[PMID: 30906473]
[http://dx.doi.org/10.1530/JOE-18-0639] [PMID: 31137012]
[http://dx.doi.org/10.1016/j.cbi.2019.03.012] [PMID: 30885636]
[http://dx.doi.org/10.1016/j.peptides.2014.08.014] [PMID: 25195184]
[http://dx.doi.org/10.1016/j.neuropharm.2014.07.015] [PMID: 25107586]
[http://dx.doi.org/10.1016/j.bbrc.2018.11.135] [PMID: 30553453]
[http://dx.doi.org/10.1016/j.bbrc.2017.11.114] [PMID: 29175324]
[http://dx.doi.org/10.1016/j.intimp.2019.105732] [PMID: 31336333]
[http://dx.doi.org/10.1080/21691401.2019.1620248] [PMID: 31174433]
[http://dx.doi.org/10.1016/j.ejphar.2016.02.003] [PMID: 26849938]
[http://dx.doi.org/10.1371/journal.pone.0158205] [PMID: 27421117]
[http://dx.doi.org/10.2147/CPAA.S164785] [PMID: 30349407]
[http://dx.doi.org/10.7573/dic.212283] [PMID: 26213556]
[PMID: 20975810]
[http://dx.doi.org/10.1111/j.1463-1326.2010.01212.x] [PMID: 20590741]
[http://dx.doi.org/10.1111/1440-1681.12455] [PMID: 26173919]
[http://dx.doi.org/10.4239/wjd.v9.i10.165] [PMID: 30364744]
[PMID: 24304575]
[http://dx.doi.org/10.1111/dom.12432] [PMID: 25580570]
[http://dx.doi.org/10.1080/01616412.2018.1474840] [PMID: 29781786]
[http://dx.doi.org/10.1530/JOE-12-0521] [PMID: 23591914]
[http://dx.doi.org/10.1002/ddr.21567] [PMID: 31301179]
[http://dx.doi.org/10.1155/2018/6091014] [PMID: 30186862]
[http://dx.doi.org/10.1016/j.neuint.2017.10.006] [PMID: 29032011]
[http://dx.doi.org/10.1159/000490688] [PMID: 29913457]
[http://dx.doi.org/10.2174/1871527315666161003125752] [PMID: 27697060]
[http://dx.doi.org/10.1111/jdi.12847] [PMID: 29607626]
[http://dx.doi.org/10.3892/etm.2018.6016] [PMID: 29805536]
[PMID: 29257340]
[http://dx.doi.org/10.1016/j.taap.2017.08.005] [PMID: 28807765]
[http://dx.doi.org/10.4172/2329-6607.1000203]
[http://dx.doi.org/10.1186/s13098-015-0087-3] [PMID: 26500706]
[http://dx.doi.org/10.1016/j.diabres.2016.12.010] [PMID: 28056430]
[http://dx.doi.org/10.1210/jc.2009-0473] [PMID: 19892839]
[http://dx.doi.org/10.3310/hta21020] [PMID: 28105986]
[http://dx.doi.org/10.1007/s40265-018-0878-6] [PMID: 29476348]
[http://dx.doi.org/10.2174/18715273113126660160] [PMID: 24059302]
[http://dx.doi.org/10.1002/bab.1319] [PMID: 25402624]
[http://dx.doi.org/10.1016/j.cbi.2017.08.013] [PMID: 28837785]
[http://dx.doi.org/10.1038/s41598-019-46402-6] [PMID: 31285506]
[http://dx.doi.org/10.1186/s12933-014-0148-1] [PMID: 25344694]
[http://dx.doi.org/10.1016/j.ejphar.2016.11.028] [PMID: 27876617]
[http://dx.doi.org/10.1530/JOE-17-0263] [PMID: 28611211]
[http://dx.doi.org/10.4155/fmc-2018-0514] [PMID: 31161798]
[http://dx.doi.org/10.1021/cn100008c] [PMID: 22778837]
[http://dx.doi.org/10.1016/j.jss.2015.09.035] [PMID: 26850186]
[http://dx.doi.org/10.1161/ATVBAHA.115.307011] [PMID: 26769045]
[http://dx.doi.org/10.2174/0929867324666170116125159] [PMID: 28093982]
[http://dx.doi.org/10.2174/1389450119666180808105056] [PMID: 30091414 ]
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