Abstract
Alzheimer's Disease (AD) is one of the most important neurodegenerative diseases, accounting for 60% of all dementia cases. AD is a progressive neurodegenerative disease that occurs due to the production of β-amyloid (Aβ) protein and accumulation of hyper-phosphorylated tau protein; it causes breakage in the synaptic bonds and neuronal deaths to a large extent. Millions of people worldwide suffer from AD because there is no definitive drug for disease prevention, treatment, or slowing down its progression. Over the last decade, multiple target applications have been developed for AD treatments. These targets include Aβ accumulations, hyper-phosphorylated tau proteins, mitochondrial dysfunction, and oxidative stress, resulting in toxicity. Various natural or semisynthetic antioxidant formulations have been shown to protect brain cells from Aβ-induced toxicity and provide promising potentials for AD treatment. Ferulic acid (FA), a high-capacity antioxidant molecule, is naturally synthesized from certain plants. FA has been shown to have different substantial biological properties, such as anticancer, antidiabetic, antimicrobial, anti-inflammatory, hepatoprotective, and cardioprotective actions, etc. Furthermore, FA exerts neuroprotection via preventing Aβ-fibril formation, acting as an anti-inflammatory agent, and inhibiting free radical generation and acetylcholinesterase (AChE) enzyme activity. In this review, we present key biological roles of FA and several FA derivatives in preventing Aβ-induced neurotoxicity, protecting against free radical attacks, and exhibiting enzyme inhibitions and evaluate them as possible therapeutic agents for the treatment of AD.
Keywords: Ferulic acid, anti-Alzheimer, Alzheimer’s disease, experimental Alzheimer’s model, amyloid-beta, drug candidate, neurotoxicity, neuroprotection.
Graphical Abstract
[http://dx.doi.org/10.1111/j.0963-7214.2004.00293.x]
[http://dx.doi.org/10.1001/jamaneurol.2016.0150] [PMID: 27088644]
[http://dx.doi.org/10.1016/S0140-6736(15)01124-1] [PMID: 26921134]
[http://dx.doi.org/10.1016/j.drudis.2020.05.010] [PMID: 32442631]
[http://dx.doi.org/10.3390/biom11010126] [PMID: 33478054]
[http://dx.doi.org/10.3906/zoo-1911-32]
[http://dx.doi.org/10.1007/s00401-011-0878-z] [PMID: 21959585]
[http://dx.doi.org/10.1016/j.redox.2017.10.014] [PMID: 29080524]
[http://dx.doi.org/10.1016/j.neurobiolaging.2005.04.017] [PMID: 16481071]
[http://dx.doi.org/10.3390/biom10050737] [PMID: 32397415]
[http://dx.doi.org/10.1017/S0033583506004422] [PMID: 16978447]
[http://dx.doi.org/10.1016/j.jmb.2012.01.024] [PMID: 22321796]
[http://dx.doi.org/10.1038/416507a] [PMID: 11932737]
[http://dx.doi.org/10.1016/j.abb.2007.05.015] [PMID: 17588526]
[http://dx.doi.org/10.1063/1.3216103] [PMID: 19778093]
[http://dx.doi.org/10.3390/molecules21010053] [PMID: 26760993]
[http://dx.doi.org/10.1016/S0014-2999(02)02589-X] [PMID: 12445575]
[http://dx.doi.org/10.2174/1567201816666191022105036] [PMID: 31642410]
[http://dx.doi.org/10.1016/j.ejmech.2019.111880] [PMID: 31753513]
[http://dx.doi.org/10.1007/s12640-019-00130-x] [PMID: 31802378]
[http://dx.doi.org/10.1016/j.bmcl.2018.11.057] [PMID: 30522955]
[http://dx.doi.org/10.1016/j.npep.2017.09.001] [PMID: 28993014]
[http://dx.doi.org/10.1016/j.etp.2010.03.004] [PMID: 20346638]
[http://dx.doi.org/10.1080/00207454.2020.1754211] [PMID: 32308094]
[http://dx.doi.org/10.1007/s11030-016-9715-6] [PMID: 28050687]
[http://dx.doi.org/10.2174/1567201814666171013150534] [PMID: 29034836]
[http://dx.doi.org/10.1021/acscombsci.6b00116] [PMID: 28045249]
[http://dx.doi.org/10.1038/nrd.2015.21] [PMID: 26794270]
[http://dx.doi.org/10.3390/ijms17071035] [PMID: 27376271]
[http://dx.doi.org/10.1016/j.ejmech.2014.11.012] [PMID: 25461306]
[http://dx.doi.org/10.1002/sscp.201900038]
[http://dx.doi.org/10.1159/000491755] [PMID: 30235459]
[http://dx.doi.org/10.1016/j.jnutbio.2017.06.011] [PMID: 28759787]
[PMID: 27830004]
[http://dx.doi.org/10.1139/apnm-2015-0002] [PMID: 26201855]
[http://dx.doi.org/10.1111/jfbc.13505] [PMID: 33047361]
[http://dx.doi.org/10.3389/fninf.2018.00031] [PMID: 29896095]
[http://dx.doi.org/10.1016/j.neuro.2019.04.006] [PMID: 31029786]
[http://dx.doi.org/10.1523/JNEUROSCI.6357-11.2012] [PMID: 22378880]
[http://dx.doi.org/10.1016/j.brainres.2008.02.090] [PMID: 18400211]
[http://dx.doi.org/10.1038/sj.bjp.0704047] [PMID: 11325798]
[http://dx.doi.org/10.1016/j.fct.2020.111808] [PMID: 33045309]
[http://dx.doi.org/10.1016/j.biomaterials.2013.11.074] [PMID: 24332460]
[http://dx.doi.org/10.1016/j.colsurfb.2013.04.005] [PMID: 23668982]
[http://dx.doi.org/10.1080/10715760903214454] [PMID: 19863373]
[http://dx.doi.org/10.2174/157341309787314656]
[http://dx.doi.org/10.1016/j.fct.2013.12.024] [PMID: 24373826]
[http://dx.doi.org/10.3390/nu7075246] [PMID: 26184304]
[http://dx.doi.org/10.1007/s10522-008-9160-8] [PMID: 18651237]
[http://dx.doi.org/10.1016/j.jff.2015.06.018]
[http://dx.doi.org/10.1016/j.foodchem.2005.07.042]
[http://dx.doi.org/10.1093/jn/134.4.785] [PMID: 15051826]
[http://dx.doi.org/10.1039/D0FO00800A] [PMID: 32409814]
[http://dx.doi.org/10.1016/j.bjp.2015.08.013]
[http://dx.doi.org/10.4103/2231-0738.139400]
[http://dx.doi.org/10.1016/j.jnutbio.2009.04.001] [PMID: 19443196]
[http://dx.doi.org/10.1111/j.1742-481X.2012.01119.x] [PMID: 23236955]
[http://dx.doi.org/10.1007/s12020-012-9868-8] [PMID: 23299178]
[http://dx.doi.org/10.1016/j.mrfmmm.2005.06.012] [PMID: 16085126]
[http://dx.doi.org/10.1111/j.1471-4159.2004.02899.x] [PMID: 15686476]
[http://dx.doi.org/10.1016/j.neuint.2005.11.006] [PMID: 16386335]
[http://dx.doi.org/10.1016/S0955-2863(01)00215-7] [PMID: 12015157]
[http://dx.doi.org/10.1111/j.1472-8206.2005.00332.x] [PMID: 16011737]
[http://dx.doi.org/10.1016/j.pnpbp.2005.04.022] [PMID: 15970368]
[http://dx.doi.org/10.1016/j.intimp.2019.105980] [PMID: 31699670]
[http://dx.doi.org/10.1016/j.fct.2010.05.063] [PMID: 20573577]
[http://dx.doi.org/10.1080/01635581.2011.538486] [PMID: 21500097]
[http://dx.doi.org/10.1021/jf060899p] [PMID: 16848520]
[http://dx.doi.org/10.1097/FJC.0b013e31827cb600] [PMID: 23188120]
[http://dx.doi.org/10.1016/j.ejphar.2012.05.019] [PMID: 22659112]
[http://dx.doi.org/10.1007/s11033-020-05896-4] [PMID: 33040267]
[http://dx.doi.org/10.1385/BTER:85:2:183] [PMID: 11899025]
[http://dx.doi.org/10.1016/j.jpba.2020.113643] [PMID: 33002782]
[http://dx.doi.org/10.3390/biom10091323] [PMID: 32942739]
[http://dx.doi.org/10.1016/j.bbrc.2005.08.148] [PMID: 16153607]
[http://dx.doi.org/10.1248/bpb.27.120] [PMID: 14709913]
[http://dx.doi.org/10.1007/s11064-011-0580-5] [PMID: 21858698]
[http://dx.doi.org/10.1111/j.1474-9726.2008.00423.x] [PMID: 18691184]
[http://dx.doi.org/10.2741/2130] [PMID: 17127365]
[http://dx.doi.org/10.1142/S0192415X15500214] [PMID: 25807957]
[http://dx.doi.org/10.1007/s00044-018-2178-9] [PMID: 29937677]
[http://dx.doi.org/10.1016/j.ejmech.2019.07.011] [PMID: 31301562]
[http://dx.doi.org/10.1248/bpb.b12-00798] [PMID: 23075678]
[http://dx.doi.org/10.1248/bpb.b19-00332] [PMID: 31582657]
[http://dx.doi.org/10.1016/j.neulet.2011.12.012] [PMID: 22200499]
[http://dx.doi.org/10.1016/j.neuroscience.2009.10.023] [PMID: 19837139]
[http://dx.doi.org/10.1371/journal.pone.0055774] [PMID: 23409038]
[http://dx.doi.org/10.1016/j.bmcl.2016.03.086] [PMID: 27072909]
[http://dx.doi.org/10.1016/j.ejmech.2017.02.039] [PMID: 28279845]
[http://dx.doi.org/10.4155/fmc.14.148] [PMID: 25582330]
[http://dx.doi.org/10.1002/cmdc.201402409] [PMID: 25537267]
[http://dx.doi.org/10.1016/j.bioorg.2019.103506] [PMID: 31887472]
[http://dx.doi.org/10.4155/fmc-2019-0191] [PMID: 31838896]
[http://dx.doi.org/10.1074/jbc.RA118.004280] [PMID: 30563837]
[http://dx.doi.org/10.1016/j.ejphar.2016.04.047] [PMID: 27118174]
[http://dx.doi.org/10.1016/j.bioorg.2019.103413] [PMID: 31791679]
[http://dx.doi.org/10.1021/acschemneuro.8b00530] [PMID: 30537804]
[http://dx.doi.org/10.1039/C6MD00053C]
[http://dx.doi.org/10.1080/14786419.2016.1219862] [PMID: 27531418]
[http://dx.doi.org/10.1016/j.bioorg.2019.103310] [PMID: 31586704]
[http://dx.doi.org/10.1080/14756366.2018.1430691] [PMID: 29405075]
[http://dx.doi.org/10.1111/cns.12010] [PMID: 23106978]
[http://dx.doi.org/10.2147/IJN.S87148] [PMID: 26345528]
[http://dx.doi.org/10.3390/molecules180910747] [PMID: 24005968]
[http://dx.doi.org/10.1016/j.nano.2012.05.007] [PMID: 22640910]
[http://dx.doi.org/10.1186/s11671-018-2638-7] [PMID: 30097809]
[http://dx.doi.org/10.1016/j.ijpharm.2015.03.001] [PMID: 25747452]
[http://dx.doi.org/10.1088/1361-6528/28/2/025102] [PMID: 27922827]
[http://dx.doi.org/10.3892/br.2016.630] [PMID: 27123241]
[http://dx.doi.org/10.1016/j.lfs.2017.11.046] [PMID: 29196052]
[http://dx.doi.org/10.1016/j.saa.2014.03.027] [PMID: 24747845]
[http://dx.doi.org/10.1016/j.sjbs.2020.04.045] [PMID: 32565686]
[http://dx.doi.org/10.1016/j.biopha.2017.11.047] [PMID: 29136946]
[http://dx.doi.org/10.1007/s00418-020-01871-z] [PMID: 32227291]
[http://dx.doi.org/10.1016/j.lfs.2015.10.001] [PMID: 26437269]
[http://dx.doi.org/10.1021/acsanm.0c00717]
[http://dx.doi.org/10.1080/03639045.2018.1496448] [PMID: 29973105]
[http://dx.doi.org/10.1166/jbn.2019.2798] [PMID: 31219014]
[http://dx.doi.org/10.1016/j.jddst.2020.101854]
[http://dx.doi.org/10.1186/s13578-015-0041-y] [PMID: 26301084]
[http://dx.doi.org/10.1038/nature04723] [PMID: 16625205]
[http://dx.doi.org/10.1038/nature05293] [PMID: 17051206]
[http://dx.doi.org/10.1111/j.1460-9568.2011.07613.x] [PMID: 21395858]
[http://dx.doi.org/10.1172/JCI33585] [PMID: 18497889]
[http://dx.doi.org/10.1002/1531-8249(200003)47:3399::AID-ANA223.0.CO;2-5] [PMID: 10716266]
[http://dx.doi.org/10.1007/s00401-013-1111-z] [PMID: 23589030]
[http://dx.doi.org/10.1038/nrd.2018.109] [PMID: 30116051]
[http://dx.doi.org/10.1002/ptr.6523] [PMID: 31657074]
[http://dx.doi.org/10.1016/j.exger.2012.07.006] [PMID: 22824543]
[http://dx.doi.org/10.1586/14737175.2015.1058160] [PMID: 26092668]
[http://dx.doi.org/10.1016/j.pneurobio.2013.06.004] [PMID: 23850509]
[http://dx.doi.org/10.1093/hmg/dds360] [PMID: 22926141]
[http://dx.doi.org/10.1093/hmg/dds360] [PMID: 22926141]
[http://dx.doi.org/10.1093/hmg/dds360] [PMID: 22926141]
[http://dx.doi.org/10.1093/hmg/dds360] [PMID: 22926141]
[http://dx.doi.org/10.1093/jnen/60.8.759] [PMID: 11487050]
[http://dx.doi.org/10.1038/nn835] [PMID: 11953750]
[http://dx.doi.org/10.1186/s40478-018-0611-4] [PMID: 30352630]
[http://dx.doi.org/10.1038/nn0408-381] [PMID: 18368041]
[http://dx.doi.org/10.1016/j.phrs.2018.11.018] [PMID: 30471405]
[http://dx.doi.org/10.1093/nar/gku1003] [PMID: 25352553]