Abstract
Background: Understanding the cognitive and behavioral aspects of Alzheimer's disease- related dementia is surely a sturdy task to deal with. In recent years, a broad search for novel anti-Alzheimer agents has been continuously conducted. The malfunctioning of various neurotransmitter systems and the accumulation of abnormal proteins in the brain are the two key characteristics of this disorder. This is supported by a growing amount of evidence. Some Pharmacophoric groups/combinations exhibit potential neuroprotective activity.
Methods: This study aims to compile the most recent and interesting target/target combinations/ pharmacophoric combinations to cure Alzheimer's disease. We concentrated our efforts to find the ability of certain pharmacophoric elements to interfere with various enzymatic and/or receptor systems or to work as neuroprotective agents. These pharmacophoric elements may be proved to be promising leads for future multi-target anti-Alzheimer drug discovery programs.
Results: Anticholinesterase drugs were mentioned as the best treatment thus far. Additionally, impairments in the serotonergic, GABAergic, noradrenergic, dopaminergic, and glutaminergic and a few other pathways have all been linked to memory, speech, behavioral and other alterations in Alzheimer's disease.
Conclusion: This includes the study of workable pharmacophoric groups/combinations, receptors/ enzymatic systems and related hypotheses to find the promising therapeutic lead compounds which could work as future anti-Alzheimer drugs. We discuss future work that would improve our understanding of this Disease.
Keywords: Alzheimer’s disease, Dementia, AD, AChE inhibitor, NMDA Receptor Antagonist, neuroprotective, Neurodegenerative disorder.
Graphical Abstract
[http://dx.doi.org/10.1017/S135561771700100X] [PMID: 29198280]
[http://dx.doi.org/10.1016/S0197-4580(98)00052-9] [PMID: 9661992]
[PMID: 34101796]
[http://dx.doi.org/10.1002/ca.980080612] [PMID: 8713166]
[http://dx.doi.org/10.1016/0028-3932(95)00046-1] [PMID: 8745122]
[http://dx.doi.org/10.1037/0033-295X.85.3.139]
[http://dx.doi.org/10.1159/000109998] [PMID: 17975326]
[http://dx.doi.org/10.1016/j.jalz.2013.02.003] [PMID: 23507120]
[http://dx.doi.org/10.1016/j.jalz.2012.11.007] [PMID: 23305823]
[http://dx.doi.org/10.1136/bmj.310.6985.970] [PMID: 7728032]
[http://dx.doi.org/10.1126/science.1074069] [PMID: 12399581]
[http://dx.doi.org/10.3390/molecules26185527] [PMID: 34576998]
[http://dx.doi.org/10.1016/j.cell.2019.09.001] [PMID: 31564456]
[http://dx.doi.org/10.1016/j.jalz.2010.11.002] [PMID: 21255746]
[http://dx.doi.org/10.3934/Neuroscience.2021005] [PMID: 33490374]
[http://dx.doi.org/10.1002/med.21699] [PMID: 32557696]
[http://dx.doi.org/10.1016/j.ejmech.2013.12.028] [PMID: 24530494]
[http://dx.doi.org/10.1016/j.bmc.2010.12.022] [PMID: 21211982]
[http://dx.doi.org/10.1006/exnr.2000.7397] [PMID: 10833325]
[http://dx.doi.org/10.1016/j.neuroscience.2012.12.054] [PMID: 23305761]
[http://dx.doi.org/10.1111/j.1471-4159.1983.tb11311.x] [PMID: 6822833]
[http://dx.doi.org/10.1016/j.ejmech.2013.03.051] [PMID: 23685572]
[http://dx.doi.org/10.1358/mf.2000.22.8.701373] [PMID: 11256231]
[http://dx.doi.org/10.2165/00023210-199912040-00005]
[http://dx.doi.org/10.3390/molecules24030587] [PMID: 30736397]
[http://dx.doi.org/10.1021/bi020016x] [PMID: 11888271]
[http://dx.doi.org/10.1034/j.1600-0404.2000.00311.x] [PMID: 11261809]
[http://dx.doi.org/10.1016/S0009-2797(99)00020-4] [PMID: 10421445]
[http://dx.doi.org/10.1016/S0021-9258(19)78115-0] [PMID: 8157652]
[http://dx.doi.org/10.1021/jm0340602] [PMID: 12773032]
[http://dx.doi.org/10.1021/jm070100g] [PMID: 17655212]
[http://dx.doi.org/10.1016/j.bmc.2010.01.071] [PMID: 20171894]
[http://dx.doi.org/10.1021/jm8001313] [PMID: 18517184]
[http://dx.doi.org/10.1021/jm060164b] [PMID: 16942022]
[http://dx.doi.org/10.1016/j.cbi.2019.05.024] [PMID: 31100281]
[http://dx.doi.org/10.1021/ja7109822] [PMID: 18512913]
[http://dx.doi.org/10.1016/j.ejmech.2014.05.056] [PMID: 24941128]
[http://dx.doi.org/10.1016/j.ejmech.2013.07.045] [PMID: 23988412]
[http://dx.doi.org/10.1016/j.ejmech.2013.03.021] [PMID: 23644208]
[http://dx.doi.org/10.1111/cbdd.12588] [PMID: 26010139]
[http://dx.doi.org/10.1002/(SICI)1099-1166(199901)14:1<3:AID-GPS897>3.0.CO;2-7] [PMID: 10029935]
[http://dx.doi.org/10.3390/ph7020113] [PMID: 24463342]
[http://dx.doi.org/10.1007/s11172-014-0561-3]
[http://dx.doi.org/10.1021/jm7009364] [PMID: 18181565]
[http://dx.doi.org/10.1586/ern.12.124] [PMID: 23234396]
[http://dx.doi.org/10.2174/0929867311320130004] [PMID: 23410164]
[http://dx.doi.org/10.1007/s11172-016-1461-5]
[http://dx.doi.org/10.1155/2020/5120230] [PMID: 32714977]
[http://dx.doi.org/10.1016/j.bmcl.2018.07.019] [PMID: 30017317]
[http://dx.doi.org/10.1016/j.ejmech.2019.07.051] [PMID: 31351393]
[http://dx.doi.org/10.1016/j.nbd.2005.09.004] [PMID: 16257224]
[http://dx.doi.org/10.1073/pnas.0813355106] [PMID: 19204293]
[http://dx.doi.org/10.1016/j.ejmech.2018.06.044] [PMID: 29958119]
[http://dx.doi.org/10.1016/j.pharmthera.2005.05.001] [PMID: 16005519]
[http://dx.doi.org/10.1021/acs.molpharmaceut.5b00830] [PMID: 26886442]
[http://dx.doi.org/10.1016/j.bmc.2010.12.055] [PMID: 21277782]
[http://dx.doi.org/10.3233/JAD-151146] [PMID: 27232215]
[http://dx.doi.org/10.3390/molecules24214009] [PMID: 31694325]
[http://dx.doi.org/10.1111/j.1476-5381.1996.tb16086.x] [PMID: 8982515]
[http://dx.doi.org/10.1016/j.bmc.2007.12.048] [PMID: 18249544]
[http://dx.doi.org/10.1021/jm701225u] [PMID: 18047264]
[http://dx.doi.org/10.1016/j.bmc.2011.09.061] [PMID: 22019465]
[http://dx.doi.org/10.1523/JNEUROSCI.1738-05.2005] [PMID: 16306398]
[http://dx.doi.org/10.1038/s41598-021-94369-0] [PMID: 34302009]
[http://dx.doi.org/10.1080/13543784.2019.1683160] [PMID: 31661331]
[http://dx.doi.org/10.1038/nm0103-3] [PMID: 12514700]
[http://dx.doi.org/10.1007/s12031-016-0800-1] [PMID: 27456313]
[http://dx.doi.org/10.3390/molecules19079307] [PMID: 24991761]
[http://dx.doi.org/10.3390/ph12010041] [PMID: 30893882]
[http://dx.doi.org/10.1056/NEJMoa1210951] [PMID: 23883379]
[http://dx.doi.org/10.1001/archneurol.2012.2194] [PMID: 22892585]
[http://dx.doi.org/10.1002/iub.1104] [PMID: 23129425]
[http://dx.doi.org/10.1152/physrev.1995.75.4.725] [PMID: 7480160]
[PMID: 17556793]
[http://dx.doi.org/10.1016/j.brainresbull.2019.09.001] [PMID: 31493542]
[http://dx.doi.org/10.1016/j.ejmech.2012.12.009] [PMID: 23313637]
[http://dx.doi.org/10.1016/j.crci.2017.07.009]
[http://dx.doi.org/10.1016/j.crci.2018.01.005]
[http://dx.doi.org/10.1038/39321] [PMID: 9335500]
[PMID: 23604855]
[http://dx.doi.org/10.1073/pnas.91.16.7787] [PMID: 8052661]
[http://dx.doi.org/10.1523/JNEUROSCI.17-08-02653.1997] [PMID: 9092586]
[http://dx.doi.org/10.1073/pnas.92.5.1794e] [PMID: 8202552]
[http://dx.doi.org/10.1126/science.1072994] [PMID: 12130773]
[http://dx.doi.org/10.1111/j.1471-4159.2004.02743.x] [PMID: 15485484]
[http://dx.doi.org/10.1016/j.ijbiomac.2012.04.012] [PMID: 22542854]
[http://dx.doi.org/10.1002/cbf.290040202] [PMID: 3518979]
[http://dx.doi.org/10.1038/nrn1883] [PMID: 16552415]
[http://dx.doi.org/10.1007/s00702-003-0828-6] [PMID: 12811639]
[http://dx.doi.org/10.1038/nchembio0215-172c]
[http://dx.doi.org/10.1038/sj.bjp.0706464] [PMID: 16402116]
[http://dx.doi.org/10.1021/jm3015926] [PMID: 23458846]
[http://dx.doi.org/10.1042/bj0220968] [PMID: 16744124]
[http://dx.doi.org/10.1016/j.ejmech.2020.112787] [PMID: 32942081]
[http://dx.doi.org/10.1080/14756366.2019.1574297] [PMID: 30746966]
[http://dx.doi.org/10.1016/j.ejmech.2019.07.031] [PMID: 31325784]
[http://dx.doi.org/10.1212/WNL.48.3.626] [PMID: 9065537]
[http://dx.doi.org/10.1212/WNL.54.2.295] [PMID: 10668686]