Gut Inflammation in Association With Pathogenesis of Parkinson's Disease

Abstract

Parkinson's disease (PD) is a neurodegenerative disease that is generally thought to be caused by multiple factors, including environmental and genetic factors. Emerging evidence suggests that intestinal disturbances, such as constipation, are common non-motor symptoms of PD. Gut inflammation may be closely associated with pathogenesis in PD. This review aims to discuss the cross-talk between gut inflammation and PD pathology initiation and progression. Firstly, we will highlight the studies demonstrating how gut inflammation is related to PD. Secondly, we will analyze how gut inflammation spreads from the gastro-intestine to the brain. Here, we will mainly discuss the neural pathway of pathologic α-syn and the systemic inflammatory routes. Thereafter, we will address how alterations in the brain subsequently lead to dopaminergic neuron degeneration, in which oxidative stress, glutamate excitotoxicity, T cell driven inflammation and cyclooxygenase-2 (COX-2) are involved. We conclude a model of PD triggered by gut inflammation, which provides a new angle to understand the mechanisms of the disease.

Keywords: Parkinson’s disease; T-cell; cyclooxygenase-2; glutamate excitotoxicity; gut inflammation; oxidative stress; α-synuclein.

FIGURE 1

Possible pathways involved in gut inflammation induced neuron death in the brain. Gut inflammation may increase intestinal permeability, allowing the leakage of bacteria and their metabolites which may trigger pathologic α-syn aggregation and pro-inflammatory cytokine production and release in the ENS. Pathologic α-syn is propagated to the brain via the vagal nerve, and inflammatory cytokines are transported to the brain through the humoral pathway or stimulate the vagal nerve to produce pro-inflammatory factors in the brain. Pro-inflammatory cytokines and synucleinopathies in the brain may induce neuronal injury and death, which in turn enhance more severe inflammatory responses.