Login Register Cart 0
Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

In Silico Docking of Novel Phytoalkaloid Camalexin in the Management of Benomyl Induced Parkinson's Disease and its In Vivo Evaluation by Zebrafish Model

Author(s): Tamilanban Thamaraikani, Manasa Karnam* and Chitra Velapandian

Volume 21, Issue 4, 2022

Published on: 03 September, 2021

Page: [343 - 353] Pages: 11

DOI: 10.2174/1871527320666210903091447

Price: $65

conference banner
Abstract

Background: Parkinson’s Disease (PD) exhibits the extrapyramidal symptoms caused due to the dopaminergic neuronal degeneration in the substantia nigra of the brain and depletion of Aldehyde Dehydrogenase (ALDH) enzyme.

Objective: This study was designed to enlighten the importance of the Aldehyde dehydrogenase enzyme in protecting the dopamine levels in a living system. Camalexin, a potentially active compound, has been evaluated for its dopamine enhancing and aldehyde dehydrogenase protecting role in pesticide-induced Parkinson’s disease.

Methods: AutoDock 4.2 software was employed to perform the docking simulations between the ligand camalexin and standard drugs Alda-1, Ropirinole with three proteins 4WJR, 3INL, 5AER. Consequently, the compound was evaluated for its in vivo neuroprotective role in the zebrafish model by attaining Institutional Animal Ethical Committee permission. The behavioral assessments and catecholamine analysis in zebrafish were performed.

Results: The Autodock result shows that the ligand camalexin has a lower binding energy (-3.84) that indicates a higher affinity with the proteins when compared to the standard drug of proteins (-3.42). In the zebrafish model, behavioral studies provided evidence that camalexin helps in the improvement of motor functions and cognition. The catecholamine assay has proved that there is an enhancement in dopamine levels, as well as an improvement in aldehyde dehydrogenase enzyme.

Conclusion: The novel compound, camalexin, offers a protective role in Parkinson’s disease model by its interaction with neurochemical proteins and also in alternative in vivo model.

Keywords: Camalexin, Autodock 4.2, Alda-1, aldehyde dehydrogenase, benomyl, Parkinson’s disease.

« Previous Next »
Graphical Abstract

[1]
Sulzer D, Surmeier DJ. Neuronal vulnerability, pathogenesis, and Parkinson’s disease. Mov Disord 2013; 28(1): 41-50.
[http://dx.doi.org/10.1002/mds.25095] [PMID: 22791686]
[2]
Kamel F, Hoppin JA. Association of pesticide exposure with neurologic dysfunction and disease. Environ Health Perspect 2004; 112(9): 950-8.
[http://dx.doi.org/10.1289/ehp.7135] [PMID: 15198914]
[3]
Burke WJ, Li SW, Williams EA, Nonneman R, Zahm DS. 3,4-Dihydroxyphenylacetaldehyde is the toxic dopamine metabolite in vivo: implications for Parkinson’s disease pathogenesis. Brain Res 2003; 989(2): 205-13.
[http://dx.doi.org/10.1016/S0006-8993(03)03354-7] [PMID: 14556942]
[4]
Marchitti SA, Deitrich RA, Vasiliou V. Neurotoxicity and metabolism of the catecholamine-derived 3,4-dihydroxyphenylacetaldehyde and 3,4-dihydroxyphenylglycolaldehyde: the role of aldehyde dehydrogenase. Pharmacol Rev 2007; 59(2): 125-50.
[http://dx.doi.org/10.1124/pr.59.2.1] [PMID: 17379813]
[5]
Fitzmaurice AG, Rhodes SL, Cockburn M, Ritz B, Bronstein JM. Aldehyde dehydrogenase variation enhances effect of pesticides associated with Parkinson disease. Neurology 2014; 82(5): 419-26.
[http://dx.doi.org/10.1212/WNL.0000000000000083] [PMID: 24491970]
[6]
Casida JE, Ford B, Jinsmaa Y, Sullivan P, Cooney A, Goldstein DS. Benomyl, aldehyde dehydrogenase, DOPAL, and the catecholaldehyde hypothesis for the pathogenesis of Parkinson’s disease. Chem Res Toxicol 2014; 27(8): 1359-61.
[http://dx.doi.org/10.1021/tx5002223] [PMID: 25045800]
[7]
Kirch HH, Schlingensiepen S, Kotchoni S, Sunkar R, Bartels D. Detailed expression analysis of selected genes of the aldehyde dehydrogenase (ALDH) gene superfamily in Arabidopsis thaliana. Plant Mol Biol 2005; 57(3): 315-32.
[http://dx.doi.org/10.1007/s11103-004-7796-6] [PMID: 15830124]
[8]
Yang Y, Wang G, Wu W, et al. Camalexin induces apoptosis via the ROS-ER stress-mitochondrial apoptosis pathway in AML cells. Oxid Med Cell Longev 2018; 2018: 7426950.
[http://dx.doi.org/10.1155/2018/7426950] [PMID: 30538806]
[9]
Stewart AM, Ullmann JFP, Norton WHJ, et al. Molecular psychiatry of zebrafish. Mol Psychiatry 2015; 20(1): 2-17.
[http://dx.doi.org/10.1038/mp.2014.128] [PMID: 25349164]
[10]
Manasa K, Chitra V, Tamilanban T. Teleost model as an alternative in parkinson’s disease. Neurol India 2020; 68(5): 979-84.
[PMID: 33109837]
[11]
Prashar P, Mahajan R, Mehta M, Satija S, Vyas M, Sharma N. Prediction of prospective anti-parkinson phytochemicals using prediction of activity spectra of substances software to justify 3R’s ethics of in-vivo evaluation. Asian J Pharm 2019; 13(3): 217.
[12]
Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010; 31(2): 455-61.
[PMID: 19499576]
[13]
Saravanan G, Panneerselvam T, Kunjiappan S, et al. Graph theoretical analysis, in silico modeling, prediction of toxicity, metabolism and synthesis of novel 2-(methyl/phenyl)-3-(4-(5-substituted-1,3,4-oxadiazol-2-yl) phenyl) quinazolin-4(3H)-ones as NMDA receptor inhibitor. Drug Dev Res 2019; 80(3): 368-85.
[http://dx.doi.org/10.1002/ddr.21511] [PMID: 30609096]
[14]
Divyashri G, Krishna Murthy TP, Sundareshan S, et al. In silico approach towards the identification of potential inhibitors from Curcuma amada Roxb against H. pylori: ADMET screening and molecular docking studies. Bioimpacts 2021; 11(2): 119-27.
[http://dx.doi.org/10.34172/bi.2021.19] [PMID: 33842282]
[15]
Bové J, Prou D, Perier C, Przedborski S. Toxin-induced models of Parkinson’s disease. NeuroRx 2005; 2(3): 484-94.
[http://dx.doi.org/10.1602/neurorx.2.3.484] [PMID: 16389312]
[16]
Zoupa M, Machera K. Zebrafish as an alternative vertebrate model for investigating developmental toxicity-the triadimefon example. Int J Mol Sci 2017; 18(4): 817.
[http://dx.doi.org/10.3390/ijms18040817] [PMID: 28417904]
[17]
Kyriakatos A, Mahmood R, Ausborn J, Porres CP, Büschges A, El Manira A. Initiation of locomotion in adult zebrafish. J Neurosci 2011; 31(23): 8422-31.
[http://dx.doi.org/10.1523/JNEUROSCI.1012-11.2011] [PMID: 21653846]
[18]
Manuel R, Gorissen M, Roca CP, et al. Inhibitory avoidance learning in zebrafish (Danio rerio): effects of shock intensity and unraveling differences in task performance. Zebrafish 2014; 11(4): 341-52.
[http://dx.doi.org/10.1089/zeb.2013.0970] [PMID: 25004302]
[19]
Seibt KJ, Oliveira RdaL, Zimmermann FF, et al. Antipsychotic drugs prevent the motor hyperactivity induced by psychotomimetic MK-801 in zebrafish (Danio rerio). Behav Brain Res 2010; 214(2): 417-22.
[http://dx.doi.org/10.1016/j.bbr.2010.06.014] [PMID: 20600350]
[20]
Yoon M, Madden MC, Barton HA. Developmental expression of aldehyde dehydrogenase in rat: a comparison of liver and lung development. Toxicol Sci 2006; 89(2): 386-98.
[http://dx.doi.org/10.1093/toxsci/kfj045] [PMID: 16291827]
[21]
Selley ML. (E)-4-hydroxy-2-nonenal may be involved in the pathogenesis of Parkinson’s disease. Free Radic Biol Med 1998; 25(2): 169-74.
[http://dx.doi.org/10.1016/S0891-5849(98)00021-5] [PMID: 9667492]
[22]
Jones LJ, McCutcheon JE, Young AMJ, Norton WHJ. Neurochemical measurements in the zebrafish brain. Front Behav Neurosci 2015; 9(246): 246.
[PMID: 26441575]
[23]
Büeler H. Impaired mitochondrial dynamics and function in the pathogenesis of Parkinson’s disease. Exp Neurol 2009; 218(2): 235-46.
[http://dx.doi.org/10.1016/j.expneurol.2009.03.006] [PMID: 19303005]
[24]
Somayajulu-Niţu M, Sandhu JK, Cohen J, et al. Paraquat induces oxidative stress, neuronal loss in substantia nigra region and parkinsonism in adult rats: neuroprotection and amelioration of symptoms by water-soluble formulation of coenzyme Q10. BMC Neurosci 2009; 10: 88-94.
[http://dx.doi.org/10.1186/1471-2202-10-88] [PMID: 19635141]
[25]
Chou AP, Li S, Fitzmaurice AG, Bronstein JM. Mechanisms of rotenone-induced proteasome inhibition. Neurotoxicol 2010; 31(4): 367-72.
[http://dx.doi.org/10.1016/j.neuro.2010.04.006] [PMID: 20417232]
[26]
Elbaz A, Levecque C, Clavel J, et al. CYP2D6 polymorphism, pesticide exposure, and Parkinson’s disease. Ann Neurol 2004; 55(3): 430-4.
[http://dx.doi.org/10.1002/ana.20051] [PMID: 14991823]
[27]
Rull RP, Ritz B. Historical pesticide exposure in California using pesticide use reports and land-use surveys: an assessment of misclassification error and bias. Environ Health Perspect 2003; 111(13): 1582-9.
[http://dx.doi.org/10.1289/ehp.6118] [PMID: 14527836]
[28]
Burgess HA, Granato M. Modulation of locomotor activity in larval zebrafish during light adaptation. J Exp Biol 2007; 210(Pt 14): 2526-39.
[http://dx.doi.org/10.1242/jeb.003939] [PMID: 17601957]
[29]
Goldstein DS, Sullivan P, Holmes C, et al. Determinants of buildup of the toxic dopamine metabolite DOPAL in Parkinson’s disease. J Neurochem 2013; 126(5): 591-603.
[http://dx.doi.org/10.1111/jnc.12345] [PMID: 23786406]
[30]
Wey MC, Fernandez E, Martinez PA, Sullivan P, Goldstein DS, Strong R. Neurodegeneration and motor dysfunction in mice lacking cytosolic and mitochondrial aldehyde dehydrogenases: implications for Parkinson’s disease. PLoS One 2012; 7(2): e31522.
[http://dx.doi.org/10.1371/journal.pone.0031522] [PMID: 22384032]
[31]
Perez-Miller S, Younus H, Vanam R, Chen CH, Mochly-Rosen D, Hurley TD. Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant. Nat Struct Mol Biol 2010; 17(2): 159-64.
[http://dx.doi.org/10.1038/nsmb.1737] [PMID: 20062057]
[32]
Zhong W, Zhang W, Li Q, et al. Pharmacological activation of aldehyde dehydrogenase 2 by Alda-1 reverses alcohol-induced hepatic steatosis and cell death in mice. J Hepatol 2015; 62(6): 1375-81.
[http://dx.doi.org/10.1016/j.jhep.2014.12.022] [PMID: 25543082]
[33]
Kabashi E, Brustein E, Champagne N, Drapeau P. Zebrafish models for the functional genomics of neurogenetic disorders. Biochim Biophys Acta 2011; 1812(3): 335-45.
[http://dx.doi.org/10.1016/j.bbadis.2010.09.011] [PMID: 20887784]
[34]
Irons TD, MacPhail RC, Hunter DL, Padilla S. Acute neuroactive drug exposures alter locomotor activity in larval zebrafish. Neurotoxicol Teratol 2010; 32(1): 84-90.
[http://dx.doi.org/10.1016/j.ntt.2009.04.066] [PMID: 19465114]
[35]
Orger MB, Gahtan E, Muto A, Page-McCaw P, Smear MC, Baier H. Behavioral screening assays in zebrafish. Methods Cell Biol 2004; 77: 53-68.
[http://dx.doi.org/10.1016/S0091-679X(04)77003-X] [PMID: 15602905]
[36]
Anderson DG, Mariappan SV, Buettner GR, Doorn JA. Oxidation of 3,4-dihydroxyphenylacetaldehyde, a toxic dopaminergic metabolite, to a semiquinone radical and an ortho-quinone. J Biol Chem 2011; 286(30): 26978-86.
[http://dx.doi.org/10.1074/jbc.M111.249532] [PMID: 21642436]
[37]
Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman ER, Mizuno Y. Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci USA 1996; 93(7): 2696-701.
[http://dx.doi.org/10.1073/pnas.93.7.2696] [PMID: 8610103]
[38]
Galter D, Buervenich S, Carmine A, Anvret M, Olson L. ALDH1 mRNA: presence in human dopamine neurons and decreases in substantia nigra in Parkinson’s disease and in the ventral tegmental area in schizophrenia. Neurobiol Dis 2003; 14(3): 637-47.
[http://dx.doi.org/10.1016/j.nbd.2003.09.001] [PMID: 14678778]
[39]
Durrenberger PF, Grünblatt E, Fernando FS, et al. Inflammatory pathways in Parkinson’s disease; A bne microarray study. Parkinsons Dis 2012; 2012: 214714.
[http://dx.doi.org/10.1155/2012/214714] [PMID: 22548201]
[40]
Scherzer CR, Eklund AC, Morse LJ, et al. Molecular markers of early Parkinson’s disease based on gene expression in blood. Proc Natl Acad Sci USA 2007; 104(3): 955-60.
[http://dx.doi.org/10.1073/pnas.0610204104] [PMID: 17215369]
[41]
Stott SR, Barker RA. Time course of dopamine neuron loss and glial response in the 6-OHDA striatal mouse model of Parkinson’s disease. Eur J Neurosci 2014; 39(6): 1042-56.
[http://dx.doi.org/10.1111/ejn.12459] [PMID: 24372914]
[42]
Solito R, Corti F, Chen CH, et al. Mitochondrial aldehyde dehydrogenase-2 activation prevents β-amyloid-induced endothelial cell dysfunction and restores angiogenesis. J Cell Sci 2013; 126(Pt 9): 1952-61.
[http://dx.doi.org/10.1242/jcs.117184] [PMID: 23447675]

Rights & Permissions Print Cite
Article Metrics
25
7
© 2024 Bentham Science Publishers | Privacy Policy