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Current Traditional Medicine

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ISSN (Print): 2215-0838
ISSN (Online): 2215-0846

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Review Article

Protective Effects of Isothiocyanates against Alzheimer's Disease

Author(s): Mohammad Asif, Chandra Kala*, Sadaf Jamal Gilani, Syed Sarim Imam, Taleuzzaman Mohamad, Farha Naaz, Iqra Rahat and Najam Ali Khan

Volume 8, Issue 3, 2022

Published on: 15 March, 2022

Article ID: e091121197839 Pages: 10

DOI: 10.2174/2215083807666211109121345

Price: $65

Abstract

Background: The extensive search for a novel therapeutic agent against Alzheimer's Disease (AD) in medical and pharmaceutical research still continues. Despite a lot being explored about its therapeutics, there is still much more to learn in order to achieve promising therapeutic agents against AD. Phytochemicals, especially secondary metabolites, are the major focus of the investigators for AD treatment.

Objective: To describe major therapeutics targets of AD and the role of isothiocyanates (ITCs) in modulating these targets.

Methods: Scientific databases, including Elsevier, Science Direct, Pub med, were explored. The explored literature was mainly journal publications on pathogenesis and targets of AD, and the effect of various ITCs in the modulation of these targets.

Results: The major targets of AD include the Nrf-2/ARE signaling pathway, MAPKs pathway, GSK-3 signaling, and Ubiquitin-Protease system. ITCs, such as Sulforaphane, Allyl isothiocyanates, Moringin, 6-(methylsulfinyl) hexyl ITC, Phenethyl isothiocyanates, and Erucin, were reported to exert a protective effect against AD via modulating one of the several above mentioned targets.

Conclusion: This article gives a detailed description of the therapeutic targets of AD and sheds light that phytochemicals, such as ITCs, can exert a protective effect against AD by targeting those pathways. However, properly designed research and clinical trials are required to include ITCs as a mainstream agent against AD.

Keywords: Alzheimer's disease, isothiocyanates, Nrf-2/ARE pathway, MAPKs signaling, ubiquitin-Protease system, sulforaphane, allyl isothiocyanates, moringin, 6-(methylsulfinyl)hexyl ITC, phenethyl isothiocyanates, erucin.

Graphical Abstract

[1]
Weller J, Budson A. Current understanding of Alzheimer's disease diagnosis and treatment. F1000 Research 2018; 7
[http://dx.doi.org/10.12688/f1000research.14506.1]
[2]
Kumar A, Singh A, Ekavali . A review on Alzheimer’s disease pathophysiology and its management: an update. Pharmacol Rep 2015; 67(2): 195-203.
[http://dx.doi.org/10.1016/j.pharep.2014.09.004] [PMID: 25712639]
[3]
DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener 2019; 14(1): 32.
[http://dx.doi.org/10.1186/s13024-019-0333-5] [PMID: 31375134]
[4]
Yiannopoulou KG, Papageorgiou SG. Current and future treatments in Alzheimer Disease: An update. J Cent Nerv Syst Dis 2020; 12: 1179573520907397.
[http://dx.doi.org/10.1177/1179573520907397] [PMID: 32165850]
[5]
D’Onofrio G, Sancarlo D, Ruan Q, et al. Phytochemicals in the treatment of Alzheimer’s disease: A systematic review. Curr Drug Targets 2017; 18(13): 1487-98.
[http://dx.doi.org/10.2174/1389450117666161102121553] [PMID: 27809746]
[6]
Kala C, Ali SS, Ahmad N, Gilani SJ. Ali, Khan, N. Isothiocyanates: A review. Res J Pharmacogn 2018; 5(2): 71-89.
[7]
Kerr F, Sofola-Adesakin O, Ivanov DK, et al. Direct Keap1-Nrf2 disruption as a potential therapeutic target for Alzheimer’s disease. PLoS Genet 2017; 13(3): e1006593.
[http://dx.doi.org/10.1371/journal.pgen.1006593] [PMID: 28253260]
[8]
Gan L, Johnson JA. Oxidative damage and the Nrf2-ARE pathway in neurodegenerative diseases. Biochim Biophys Acta 2014; 1842(8): 1208-18.
[http://dx.doi.org/10.1016/j.bbadis.2013.12.011] [PMID: 24382478]
[9]
Brandes MS, Gray NE. NRF2 as a therapeutic target in neurodegenerative diseases. ASN Neuro 2020; 12: 1759091419899782.
[http://dx.doi.org/10.1177/1759091419899782] [PMID: 31964153]
[10]
Bahn G, Jo DG. Therapeutic approaches to Alzheimer’s disease through modulation of NRF2. Neuromolecular Med 2019; 21(1): 1-11.
[http://dx.doi.org/10.1007/s12017-018-08523-5] [PMID: 30617737]
[11]
Ramsey CP, Glass CA, Montgomery MB, et al. Expression of Nrf2 in neurodegenerative diseases. J Neuropathol Exp Neurol 2007; 66(1): 75-85.
[http://dx.doi.org/10.1097/nen.0b013e31802d6da9] [PMID: 17204939]
[12]
Zhu X, Lee HG, Raina AK, Perry G, Smith MA. The role of mitogen-activated protein kinase pathways in Alzheimer’s disease. Neurosignals 2002; 11(5): 270-81.
[http://dx.doi.org/10.1159/000067426] [PMID: 12566928]
[13]
Kim EK, Choi EJ. Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta 2010; 1802(4): 396-405.
[http://dx.doi.org/10.1016/j.bbadis.2009.12.009] [PMID: 20079433]
[14]
Kremer A, Louis JV, Jaworski T, Van Leuven F. GSK3 and Alzheimer’s disease: Facts and fiction. Front Mol Neurosci 2011; 4: 17.
[http://dx.doi.org/10.3389/fnmol.2011.00017] [PMID: 21904524]
[15]
Mondragón-Rodríguez S, Perry G, Zhu X, Moreira PI, Williams S. Glycogen synthase kinase 3: A point of integration in Alzheimer’s disease and a therapeutic target? Int J Alzheimers Dis 2012; 2012: 276803.
[http://dx.doi.org/10.1155/2012/276803] [PMID: 22779025]
[16]
Oddo S. The ubiquitin-proteasome system in Alzheimer’s disease. J Cell Mol Med 2008; 12(2): 363-73.
[http://dx.doi.org/10.1111/j.1582-4934.2008.00276.x] [PMID: 18266959]
[17]
Upadhya SC, Hegde AN. Role of the ubiquitin proteasome system in Alzheimer's disease. BMC Biochem 2007; 8(Suppl 1): S12.
[http://dx.doi.org/10.1186/1471-2091-8-S1-S12]
[18]
Libro R, Giacoppo S, Soundara Rajan T, Bramanti P, Mazzon E. Natural phytochemicals in the treatment and prevention of dementia: An overview. Molecules 2016; 21(4): 518.
[http://dx.doi.org/10.3390/molecules21040518] [PMID: 27110749]
[19]
Fakhri S, Pesce M, Patruno A, et al. Attenuation of Nrf2/Keap1/ARE in Alzheimer’s disease by plant secondary metabolites: A mechanistic review. Molecules 2020; 25(21): 4926.
[http://dx.doi.org/10.3390/molecules25214926] [PMID: 33114450]
[20]
Sun Y, Yang T, Mao L, Zhang F. Sulforaphane protects against brain diseases: Roles of cytoprotective enzymes. Austin J Cerebrovasc Dis Stroke 2017; 4(1): 1054.
[PMID: 29619410]
[21]
Barančík M, Grešová L, Barteková M, Dovinová I. Nrf2 as a key player of redox regulation in cardiovascular diseases. Physiol Res 2016; 65(Suppl. 1): S1-S10.
[http://dx.doi.org/10.33549/physiolres.933403] [PMID: 27643930]
[22]
Jaafaru MS, Abd Karim NA, Enas ME, Rollin P, Mazzon E, Abdull Razis AF. Protective effect of glucosinolates hydrolytic products in Neurodegenerative Diseases (NDDs). Nutrients 2018; 10(5): 580.
[http://dx.doi.org/10.3390/nu10050580] [PMID: 29738500]
[23]
Klomparens EA, Ding Y. The neuroprotective mechanisms and effects of sulforaphane. Brain Circ 2019; 5(2): 74-83.
[http://dx.doi.org/10.4103/bc.bc_7_19] [PMID: 31334360]
[24]
Sivandzade F, Prasad S, Bhalerao A, Cucullo L. NRF2 and NF-қB interplay in cerebrovascular and neurodegenerative disorders: Molecular mechanisms and possible therapeutic approaches. Redox Biol 2019; 21: 101059.
[http://dx.doi.org/10.1016/j.redox.2018.11.017] [PMID: 30576920]
[25]
Liu Y, Hettinger CL, Zhang D, Rezvani K, Wang X, Wang H. Sulforaphane enhances proteasomal and autophagic activities in mice and is a potential therapeutic reagent for Huntington’s disease. J Neurochem 2014; 129(3): 539-47.
[http://dx.doi.org/10.1111/jnc.12647] [PMID: 24383989]
[26]
Park HM, Kim JA, Kwak MK. Protection against amyloid beta cytotoxicity by sulforaphane: role of the proteasome. Arch Pharm Res 2009; 32(1): 109-15.
[http://dx.doi.org/10.1007/s12272-009-1124-2] [PMID: 19183883]
[27]
Gan N, Wu YC, Brunet M, et al. Sulforaphane activates heat shock response and enhances proteasome activity through up-regulation of Hsp27. J Biol Chem 2010; 285(46): 35528-36.
[http://dx.doi.org/10.1074/jbc.M110.152686] [PMID: 20833711]
[28]
Angeloni C, Malaguti M, Rizzo B, Barbalace MC, Fabbri D, Hrelia S. Neuroprotective effect of sulforaphane against methylglyoxal cytotoxicity. Chem Res Toxicol 2015; 28(6): 1234-45.
[http://dx.doi.org/10.1021/acs.chemrestox.5b00067] [PMID: 25933243]
[29]
Schepici G, Bramanti P, Mazzon E. Efficacy of sulforaphane in neurodegenerative diseases. Int J Mol Sci 2020; 21(22): 8637.
[http://dx.doi.org/10.3390/ijms21228637] [PMID: 33207780]
[30]
Zhang R, Zhang J, Fang L, et al. Neuroprotective effects of sulforaphane on cholinergic neurons in mice with Alzheimer’s disease- like lesions. Int J Mol Sci 2014; 15(8): 14396-410.
[http://dx.doi.org/10.3390/ijms150814396] [PMID: 25196440]
[31]
Lee S, Kim J, Seo SG, et al. Sulforaphane alleviates scopolamine-induced memory impairment in mice. Pharmacol Res 2014; 85: 23-32.
[http://dx.doi.org/10.1016/j.phrs.2014.05.003] [PMID: 24836869]
[32]
Rajesh V, Ilanthalir S. Cognition enhancing activity of sulforaphane against scopolamine induced cognitive impairment in zebra fish (Danio rerio). Neurochem Res 2016; 41(10): 2538-48.
[http://dx.doi.org/10.1007/s11064-016-1965-2] [PMID: 27255600]
[33]
Yang W, Liu Y, Xu QQ, Xian YF, Lin ZX. Sulforaphene ameliorates neuroinflammation and hyperphosphorylated tau protein via resulating PI3K/Akt/GSK-3β pathway in experimental models of Alzheimer’s disease. Oxid Med Cell Longev 2020; 2020: 4754195.
[http://dx.doi.org/10.1155/2020/4754195] [PMID: 32963694]
[34]
Subedi L, Venkatesan R, Kim SY. Neuroprotective and anti-inflammatory activities of allyl isothiocyanate through attenuation of JNK/NF-κB/TNF-α signaling. Int J Mol Sci 2017; 18(7): 1423.
[http://dx.doi.org/10.3390/ijms18071423] [PMID: 28671636]
[35]
Xiang J, Alesi GN, Zhou N, Keep RF. Protective effects of isothiocyanates on blood-CSF barrier disruption induced by oxidative stress. Am J Physiol Regul Integr Comp Physiol 2012; 303(1): R1-7.
[http://dx.doi.org/10.1152/ajpregu.00518.2011] [PMID: 22573102]
[36]
Caglayan B, Kilic E, Dalay A, et al. Allyl isothiocyanate attenuates oxidative stress and inflammation by modulating Nrf2/HO-1 and NF-κB pathways in traumatic brain injury in mice. Mol Biol Rep 2019; 46(1): 241-50.
[http://dx.doi.org/10.1007/s11033-018-4465-4] [PMID: 30406889]
[37]
Morroni F, Sita G, Graziosi A, et al. Protective effects of 6-(Methylsulfinyl)hexyl Isothiocyanate on Aβ1-42-induced cognitive deficit, oxidative stress, inflammation, and apoptosis in mice. Int J Mol Sci 2018; 19(7): 2083.
[38]
Latronico T, Larocca M, Milella S, Fasano A, Rossano R, Liuzzi GM. Neuroprotective potential of isothiocyanates in an in vitro model of neuroinflammation. Inflammopharmacology 2020.
[39]
Zhang JY, Ding YP, Wang Z, Kong Y, Gao R, Chen G. Hydrogen sulfide therapy in brain diseases: from bench to bedside. Med Gas Res 2017; 7(2): 113-9.
[http://dx.doi.org/10.4103/2045-9912.208517] [PMID: 28744364]
[40]
Sestito S, Pruccoli L, Runfola M, et al. Design and synthesis of H2S-donor hybrids: A new treatment for Alzheimer’s disease? Eur J Med Chem 2019; 184: 111745.
[http://dx.doi.org/10.1016/j.ejmech.2019.111745] [PMID: 31585237]
[41]
Kheiri G, Dolatshahi M, Rahmani F, Rezaei N. Role of p38/MAPKs in Alzheimer’s disease: implications for amyloid beta toxicity targeted therapy. Rev Neurosci 2018; 30(1): 9-30.
[http://dx.doi.org/10.1515/revneuro-2018-0008] [PMID: 29804103]
[42]
Thakur AK, Kamboj P, Goswami K. Pathophysiology and management of Alzheimer’s disease: an overview. J Anal Pharm Res 2018; 9(2): 226-35.
[http://dx.doi.org/10.15406/japlr.2018.07.00230]
[43]
Jaja-Chimedza A, Graf BL, Simmler C, et al. Biochemical characterization and anti-inflammatory properties of an isothiocyanate-enriched moringa (Moringa oleifera) seed extract. PLoS One 2017; 12(8): e0182658.
[http://dx.doi.org/10.1371/journal.pone.0182658] [PMID: 28792522]
[44]
Tran HTT, Stetter R, Herz C, et al. Allyl Isothiocyanate: A TAS2R38 receptor-dependent immune modulator at the interface between personalized medicine and nutrition. Front Immunol 2021; 12: 669005.
[http://dx.doi.org/10.3389/fimmu.2021.669005] [PMID: 33968075]
[45]
Wang DL, Wang CY, Cao Y, et al. Allyl isothiocyanate increases MRP1 function and expression in a human bronchial epithelial cell line. Oxid Med Cell Longev 2014; 2014: 547379.
[http://dx.doi.org/10.1155/2014/547379] [PMID: 24672635]

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