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CXCR4 as possible druggable target linking inflammatory bowel disease and Parkinson's disease

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Abstract

Parkinson’s disease (PD) is a chronic, progressive, and second most prevalent neurological disorder affecting the motor system. It has been found that people suffering with inflammatory bowel disease (IBD) are at 22% more risk for PD. In the current study, we have established a molecular link between gut and brain. The microarray gene expression datasets of Homo sapiens were obtained from Gene Expression Omnibus Database. Major genes involved in gut-brain connection were found to be CXCR4, LRRK2, APOE, SNCA, IL6, HIF-1α, ABCA1 etc. The common biological pathways linking both the pathologies were found to be HIF-signaling, cytokines interactions, JAK-STAT pathway, cholesterol metabolism, apoptosis and CXCR4 signaling which modulates the synaptic function and neuronal survival in the mature brain. It is known that flavonoid-rich foods throughout life hold the potential to limit the inflammation, neurodegeneration and, to prevent the age-dependent cognitive impairment. Therefore, the potential receptor, CXCR4 was used further for docking with twenty-seven phytochemicals from 5 different classes of Flavonoids found in several dietary items. Docking studies of the top scoring compounds were compared with a known inhibitor (BPRCX807) of receptor CXCR4 (IC50 = 40.4 ± 8.0 nM). The study indicates that Flavan-3-ol families of flavonoids are the best fit and finest dietary supplements for improving brain health. Hence the food items like Pistachio nuts, hazelnuts, Green Tea, walnuts, etc. should be incorporated more in the diet of healthy people as well as in IBD and PD patients to prevent inflammation in gut and brain damage from oxidative stress.

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Acknowledgements

We acknowledge Dr. Ashok Chauhan, Founder, Amity University, for providing us infrastructure and facilities. We also acknowledge the NPDF fellowship and support given to Dr. Angamba Meetei Potshangbam by DST SERB. 

Funding

University Grant Commission (Government of India) had granted senior research fellowship to Nitu Dogra for undertaking this project (Award No:324872).

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Author notes

  1. Nitu Dogra and Ruchi Jakhmola-Mani contributed equally to this work.

Authors and Affiliations

  1. Proteomics and Translational Research Lab, Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, India, 201301

    Nitu Dogra, Ruchi Jakhmola-Mani & Deepshikha Pande Katare

  2. Department of Biotechnology, Manipur University, Canchipur, Imphal, Manipur, India, 795003

    Angamba Meetei Potshangbam

  3. Research Boulevard Technologies, Greater Noida, India, 201301

    Angamba Meetei Potshangbam

  4. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA

    Shilpa Buch

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  1. Nitu Dogra
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  4. Shilpa Buch
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  5. Deepshikha Pande Katare
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Contributions

ND, RJM and AMP have performed the experiments and wrote the manuscript. ND and RJM performed bioinformatics and network biology and AMP performed docking and simulation work. ND, RJM, AMP, SB and DPK have edited and finalized the manuscript.

N.D, R.J.M, A.M.P, S.B did the analysis and wrote the manuscript. D.P.K conceptualized the study and finalized the manuscript.

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Correspondence to Deepshikha Pande Katare.

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Dogra, N., Jakhmola-Mani, R., Potshangbam, A.M. et al. CXCR4 as possible druggable target linking inflammatory bowel disease and Parkinson's disease. Metab Brain Dis 38, 1079–1096 (2023). https://doi.org/10.1007/s11011-022-01155-6

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