Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Favorable Binding of Quercetin to α-synuclein as Potential Target in Parkinson Disease:An Insilico Approach


Affiliations
1 Department of Biomedical Science, School of Bio-Sciences and Technology, VIT University, Vellore- 632014, Tamil Nadu, India
2 Department of Biotechnology, School of Bio-Sciences and Technology, VIT University, Vellore- 632014, Tamil Nadu, India
     

   Subscribe/Renew Journal


The aim of the research is to identify possible flavonoid for the effective docking into α-Synuclein in Parkinson’s disease (PD) computationally. Flavonoids are evolving as the potential cure for the PD. α-Synuclein is one of the potential drug target involving in the death of dopaminergic neurons of Substantia Nigra Pars Compacta (SNPC) of basal ganglia in PD. In our study, molecular docking analysis were carried out on flavonoids like quercetin, epigallocatechin gallate (EGCG) and acacetin to investigate their inhibitory role and binding capability with α-Synuclein. Molecular docking experiments were performed using AutodockVina program. The Protein-Ligand interaction analysis result showed that the favorable interaction with only on quercetin and not with others. This was comparatively a strong ligand to show significant interactions with α-Synuclein with lowest binding energy. The cluster analysis of the docked conformations out of 100 runs, quercetin shows comparable higher numbers (31 conformations) with α-Synuclein. Molecular interaction of quercetin and its analogs with the potential drug target of Parkinson’s disease provides a wide scope for drug designing to combat Parkinson’s disease.

Keywords

Parkinson’s Disease, Flavonoids,α-Synuclein, Molecular Docking.
Subscription Login to verify subscription
User
Notifications
Font Size


  • Corti O, Hampe C, Darios F et al. Parkinson’s disease: from causes to mechanisms. C R Biol. 328(2); 2005: 131–142
  • Schapira AHV. Etiology of Parkinson’s disease. Neurology. 66(10);2006: S10–S23
  • Lansbury PT, Brice A. Genetics of Parkinson’s disease and biochemical studies of implicated gene products. CurrOpin Genet Dev. 12(3);2002:299–306
  • Ellis CE, Murphy EJ, Mitchell DC et al. Mitochondrial lipid abnormality and electron transport chain impairment in mice lacking alpha-synuclein. Mol Cell Biol. 25(22); 2005:10190–10201
  • Tansey MG, McCoy MK, Frank-Cannon TC. Neuroinflammatory mechanisms in Parkinson's disease: potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp Neurol. 208(1); 2007:1–25
  • Alam ZI, Jenner A, Daniel SE. Oxidative DNA damage in the parkinsonian brain: an apparent selective increase in 8-hydroxyguanine levels in substantia nigra. J Neurochem. 69(3); 1997:1196–1203
  • Blum D, Torch S, Lambeng N et al. Levodopa-induced dyskinesias in patients with Parkinson’s disease: filling the bench-to-bedside gap. Lancet Neurol. 9(11);2010:1106–1117
  • Zhu M, Han S, Fink AL. Oxidized quercetin inhibits α-synucleinfibrillization. Biochim Biophys Acta. 1830(4); 2013:2872-81
  • Mandel S, Maor G, Youdim MB. Iron and a-synuclein in the substantia nigra of MPTP-treated mice: effect of neuroprotective drugs R-apomorphine and green tea polyphenol (-)-epigallocatechin-3-gallate. J MolNeurosci 24(3);2004:401–416
  • Thompson M. ArgusLab 4.0.1., Planaria software LLC, Seattle, Wash, USA, 2004 11. Morris GM, Huey R, Lindstrom W et al. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J ComputChem 30(16);2009:2785–91
  • Trott O, Olson AJ. Auto Dock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comp Chem 31(2);2010:455-461
  • Allen D, Hunter AD. ACD/ChemSketch 1.0 (freeware); ACD/ChemSketch 2.0 and its Tautomers, Dictionary, and 3D Plug-ins; ACD/HNMR 2.0; ACD/CNMR 2.0. J Chem Educ 74;1997:905
  • Gasteiger J, Marsili M. Iterative partial equalization of orbital electro negativity a rapid access to atomic charges. Tetrahedron 36;1980:3219–28
  • Ulmer TS, Bax A, Cole NB et al. Nussbaum. Structure and Dynamics of Micelle-bound Human α-Synuclein. J BiolChem 280;2004:9595-9603
  • Muniyan R, Gurunathan J. Lauric acid and myristic acid from Allium sativum inhibit the growth of Mycobacterium tuberculosis H37Ra: in silico analysis reveals possible binding to protein kinase B. Pharmaceutical Biology. 54(12); 2011:2814-2821
  • Yamada M, Mizuno Y, Mochizuki H.Parkin gene therapy for alpha-synucleinopathy: a rat model of Parkinson's disease. Hum Gene Ther 16;2005:262–270
  • Klucken J, Shin Y, Masliah E. Hsp70 reduces alpha- synuclein aggregation and toxicity. J BiolChem 279;2004:25497–25502
  • Qiao L, Hamamichi S, Caldwell KA et al. A neuroprotective role of lysosomal enzyme cathepsin D against a-synuclein pathogenesis. MovDisord 23;2008:S8
  • Parihar MS1, Parihar A, Fujita M et al. Mitochondrial association of alpha-synuclein causes oxidative stress. Cell Mol Life Sci.65(7-8);2008:1272-84
  • Van Der Perren A, Macchi F, Dooley J et al. The role of neuroinflammation in α-synuclein-linked dopaminergic neurodegeneration in rat brain. Front. Neurosci. Conference Abstract: 11th National Congress of the Belgian Society for Neuroscience. doi: 10.3389/ 2015

Abstract Views: 16

PDF Views: 0




  • Favorable Binding of Quercetin to α-synuclein as Potential Target in Parkinson Disease:An Insilico Approach

Abstract Views: 16  |  PDF Views: 0

Authors

Himadri Shekhaar Baul
Department of Biomedical Science, School of Bio-Sciences and Technology, VIT University, Vellore- 632014, Tamil Nadu, India
Muniyan Rajiniraja
Department of Biotechnology, School of Bio-Sciences and Technology, VIT University, Vellore- 632014, Tamil Nadu, India

Abstract


The aim of the research is to identify possible flavonoid for the effective docking into α-Synuclein in Parkinson’s disease (PD) computationally. Flavonoids are evolving as the potential cure for the PD. α-Synuclein is one of the potential drug target involving in the death of dopaminergic neurons of Substantia Nigra Pars Compacta (SNPC) of basal ganglia in PD. In our study, molecular docking analysis were carried out on flavonoids like quercetin, epigallocatechin gallate (EGCG) and acacetin to investigate their inhibitory role and binding capability with α-Synuclein. Molecular docking experiments were performed using AutodockVina program. The Protein-Ligand interaction analysis result showed that the favorable interaction with only on quercetin and not with others. This was comparatively a strong ligand to show significant interactions with α-Synuclein with lowest binding energy. The cluster analysis of the docked conformations out of 100 runs, quercetin shows comparable higher numbers (31 conformations) with α-Synuclein. Molecular interaction of quercetin and its analogs with the potential drug target of Parkinson’s disease provides a wide scope for drug designing to combat Parkinson’s disease.

Keywords


Parkinson’s Disease, Flavonoids,α-Synuclein, Molecular Docking.

References