Crosstalk between Inflammatory Bowel Disease Proteins and Neuroinflammatory Proteins for Understanding Involvement of Gut-Brain Axis in Parkinson’s Disease and Identified Drug Receptors: In-Silico Approach

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 22% more prone to PD. In the current study, we have framed a hypothesis and deciphered protein-protein interaction network between the IBD and PD and therefore, have proposed a role of gut-brain axis in PD. Text mining for retrieval of Differentially Expressed protein (DEPs; specific to Homo sapiens) associated with PD and IBD was done using Science Direct, Pub Med Central, Sci ELO and JSTOR. The protein interaction network was constructed in Cytoscape (version 3.7.1) by using above 58 DEPs. The generated master network was further analyzed using BiNGO plugin for retrieval of overrepresented biological processes in IBD-PD pathologies. Hub nodes were also generated in the network. In the present study the gutbrain hypothesis was designed which demonstrates the series of protein interactions that ought to link IBD to PD. Major proteins involved in this connection were LRRK2, APOE, SNCA, IL6, HIF-1α, ABCA, TLR4, CREB1, IL10, ADORA2A, DRD2, INOS, CCL2, SLC6A3 and CASP3. These proteins could be used as druggable targets to halt the progression of PD pathogenesis initiating via IBD. The common biological pathways linking both the pathologies were found to be HIF-signaling, Cytokines interactions, JAK-STAT pathway, Cholesterol metabolism, cAMP mediated signaling and apoptosis. This study also suggests the role ABC transporters and APOE in linking IBD and PD via disturbance of cerebral homeostasis.