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

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.

Keywords: Gene interaction networks; Gut-Brain axis; In-silico analysis; Molecular docking; Theaflavin-3’-O gallate.