Molecular Communication Between Neuronal Networks and Intestinal Epithelial Cells in Gut Inflammation and Parkinson's Disease

Abstract

Intestinal symptoms, such as nausea, vomiting, and constipation, are common in Parkinson's disease patients. These clinical signs normally appear years before the diagnosis of the neurodegenerative disease, preceding the occurrence of motor manifestations. Moreover, it is postulated that Parkinson's disease might originate in the gut, due to a response against the intestinal microbiota leading to alterations in alpha-synuclein in the intestinal autonomic nervous system. Transmission of this protein to the central nervous system is mediated potentially via the vagus nerve. Thus, deposition of aggregated alpha-synuclein in the gastrointestinal tract has been suggested as a potential prodromal diagnostic marker for Parkinson's disease. Interestingly, hallmarks of chronic intestinal inflammation in inflammatory bowel disease, such as dysbiosis and increased intestinal permeability, are also observed in Parkinson's disease patients. Additionally, alpha-synuclein accumulations were detected in the gut of Crohn's disease patients. Despite a solid association between neurodegenerative diseases and gut inflammation, it is not clear whether intestinal alterations represent cause or consequence of neuroinflammation in the central nervous system. In this review, we summarize the bidirectional communication between the brain and the gut in the context of Parkinson's disease and intestinal dysfunction/inflammation as present in inflammatory bowel disease. Further, we focus on the contribution of intestinal epithelium, the communication between intestinal epithelial cells, microbiota, immune and neuronal cells, as well as mechanisms causing alterations of epithelial integrity.

Association Analysis of WNT3, HLA-DRB5 and IL1R2 Polymorphisms in Chinese Patients With Parkinson’s Disease and Multiple System Atrophy

“…The locus rs2074404 of WNT3 was previously found to be a CD (Coeliac disease) associated polymorphism ( Dubois et al, 2010 ; Franke et al, 2010 ; Amundsen et al, 2014 ). It was also shown that gut inflammation is a main pathological feature occurring in both PD and CD and this inflammation may contribute to α-synuclein aggregation ( Dzamko et al, 2017 ; Drobny et al, 2021 ). Additionally, some SNPs in genes responsible for binding bacterial metabolites and intestinal homeostasis were associated with PD ( Gorecki et al, 2020 ).…”

Simulate the Dynamic Interactions Across Nutritional Supplements, the Polybiome, and the Biochemical Approach Dependent on Patient-Derived Gastrointestinal Knowledge

“…The fatality rate rises as a result of this illness. Many various types of bodily fluids, such as blood and tissue, as well as the beneficial bacteria that are prevalent in large bowel ecosystems, have been the primary focus of recent investigations [220][221][222][223]. The majority of studies have focused on the beneficial microorganisms that naturally occur in the colon.…”

Neuroinflammation and Parkinson’s Disease—From Neurodegeneration to Therapeutic Opportunities

“…This coincides with a work reporting that in PD patients, activated microglia closely interact with neurons presenting α-Syn pathological accumulation [ 113 ]. Similarly, direct administration of extracellular α-Syn primes the microglia and makes them susceptible to proinflammatory environmental challenge [ 114 ], inducing intracellular signaling cascades and modulating inflammatory cytokine production [ 115 ] ( Figure 2 A). However, it should be noted that microglia can also deal with α-Syn during cell-clearing processes [ 116 ].…”