AN IN SILICO STUDY OF NARINGENIN-MEDIATED NEUROPROTECTION IN PARKINSON'S DISEASE

  • Saurabh Kumar Jha Department of Biotechnology, Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi -
  • Pravir Kumar Department of Biotechnology, Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi - http://orcid.org/0000-0001-7444-2344

Abstract

 

 Objective: Naringenin is a dietary biomolecule with broad spectrum of activities which protects neurons from various neurotoxic insults and improves cognition and motor function in neurodegenerative diseases. DJ-1 has both, ubiquitin E3 ligase as well as chaperonic activity, and loss of ubiquitin E3 ligase activity of DJ-1 has been found to be associated with familial Parkinson's disease (PD). Naringenin induced E3 ligase activity of DJ-1 which can have possible clinical relevance in PD.

Methods: Various in silico parameters such as phylogenetic analysis, homology modeling, active site prediction, and molecular docking studies using AutoDock 4.2.1 and LIGPLOT1.4.5 were carried out.

Results: Three-dimensional structure of DJ-1 was generated and Ramachandran plot was obtained for quality assessment. RAMPAGE displayed 99.5% of residues in the most favored regions. 0% residues in additionally allowed and 0.5% disallowed regions of DJ-1 protein. Further, initial screenings of the molecules were done based on Lipinski's rule of five. CastP server used to predict the ligand binding site suggests that this protein can be utilized as a potential drug target. Finally, we have found naringenin to be most effective among four biomolecules in modulating DJ-1 based on minimum inhibition constant, Ki, and highest negative free energy of binding with maximum interacting surface area in the course of docking studies.

Conclusion: Our study suggests that based on different in silico parameters and molecular docking studies, naringenin can provide a new avenue for PD therapeutics.

Keywords: Parkinson’s disease, Ubiquitin E3 ligase, DJ-1, Molecular docking, Naringenin.

Author Biographies

Saurabh Kumar Jha, Department of Biotechnology, Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi -

Molecular Neuroscience and Functional Genomics Laboratory,

Department of Biotechnology

PhD student

Pravir Kumar, Department of Biotechnology, Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi -

Associate Professor at Delhi Technological University (Former Delhi College of Engineering);

Ex-Faculty, Neurology Depaertment, Tufts University School of Medicine, Boston, MA USA

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Jha, S. K., and P. Kumar. “AN IN SILICO STUDY OF NARINGENIN-MEDIATED NEUROPROTECTION IN PARKINSON’S DISEASE”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 10, no. 8, Aug. 2017, pp. 171-6, doi:10.22159/ajpcr.2017.v10i8.18709.
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