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Molecular docking studies of natural immunomodulators indicate their interactions with the CD40L of CD40/CD40L pathway and CSF1R kinase domain of microglia

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Abstract

Natural products have proved beneficial in reducing neuroinflammation in neurological diseases. Their impacts have also been associated with the activities of microglia, responsible for brain-specific immunity. Recent studies have shown the involvement of the number of microglia-specific proteins in the regulation of brain-specific immunity. However, molecular targets of natural products and their mechanism of interaction with microglia-specific proteins are elusive. Since the genetic signature of microglia offers many potential targets for drug discovery, molecular docking followed by molecular dynamics (MD) simulations of cluster of differentiation 40 ligand (CD40L) and colony-stimulating factor 1 receptor (CSF1R) kinase domain protein with some known neuro-immunomodulators (Curcumin, Cannabidiol, Ginsenoside Rg1, Resveratrol, and Sulforaphane) has been evaluated. Curcumin and cannabidiol were observed likely to modulate CD40L and expression of cytokines and entry of inflammatory cells. Resveratrol and cannabidiol may affect the CSF1R kinase domain and activation of microglia. Our finding suggests that curcumin, cannabidiol, and resveratrol may serve specific drug ligands in regulating microglia-mediated brain immunity.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

SKM acknowledges Ramjas College, University of Delhi, Delhi for its continuous support and motivation.

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Authors and Affiliations

  1. Department of Zoology, Ramjas College, University of Delhi, 110007, Delhi, India

    Shashank Kumar Maurya

  2. Department of Zoology, School of Sciences, Cluster University of Jammu, 180001, Jammu, India

    Shashank Kumar Maurya

  3. Biochemistry and Molecular Biology Laboratory, Department of Zoology, Banaras Hindu University, 221005, Varanasi, India

    Shashank Kumar Maurya & Rajnikant Mishra

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  1. Shashank Kumar Maurya
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SKM and RM conceptualized the manuscript. SKM performed the experiments and wrote the initial draft of the manuscript. RM supervised the study, reviewed, and edited the manuscript. All the authors approved the manuscript before submission.

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Correspondence to Rajnikant Mishra.

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Maurya, S.K., Mishra, R. Molecular docking studies of natural immunomodulators indicate their interactions with the CD40L of CD40/CD40L pathway and CSF1R kinase domain of microglia. J Mol Model 28, 101 (2022). https://doi.org/10.1007/s00894-022-05084-0

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