Inflammatory Bowel Diseases and Parkinson’s Disease

Abstract

The etiology of Parkinson's disease (PD) is multifactorial, with genetics, aging, and environmental agents all a part of the PD pathogenesis. Widespread aggregation of the ␣-synuclein protein in the form of Lewy bodies and Lewy neurites, and degeneration of substantia nigra dopamine neurons are the pathological hallmarks of PD. Inflammatory responses manifested by glial reactions, T cell infiltration, and increased expression of inflammatory cytokines, as well as other toxic mediators derived from activated glial cells, are currently recognized as prominent features of PD. Experimental, clinical and epidemiological data suggest that intestinal inflammation contributes to the pathogenesis of PD, and the increasing number of studies suggests that the condition may start in the gastrointestinal system years before any motor symptoms develop. Patients with inflammatory bowel disease (IBD) have a higher risk of developing PD compared with non-IBD individuals. Gene association study has found a genetic link between IBD and PD, and an evidence from animal studies suggests that gut inflammation, similar to that observed in IBD, may induce loss of dopaminergic neurons. Based on preclinical models of PD, it is suggested that the enteric microbiome changes early in PD, and gut infections trigger ␣-synuclein release and aggregation. In this paper, the possible link between IBD and PD is reviewed based on the available literature. Given the potentially critical role of gastrointestinal pathology in PD pathogenesis, there is reason to suspect that IBD or its treatments may impact PD risk. Thus, clinicians should be aware of PD symptoms in IBD patients.

Nuclear Factor-κB Dysregulation and α-Synuclein Pathology: Critical Interplay in the Pathogenesis of Parkinson’s Disease

“…Either innate or adaptive immune responses are implicated in PD (Kannarkat et al, 2013;Sulzer et al, 2017;Kustrimovic et al, 2019;Li et al, 2019;Tansey and Romero-Ramos, 2019). PD patients exhibit both brain and peripheral inflammation, and it has been found that inflammatory bowel disease predisposes to PD (Brudek, 2019). Notably, neuroinflammation promotes α-syn prion-like behavior, and along with aging, both the gastrointestinal tract and olfactory epithelium, which have been proposed as the initiation sites for α-syn spreading in the prion hypothesis, are mostly vulnerable to inflammation (Lema Tome et al, 2013).…”

Neuroinflammatory Remodeling of the Anterior Cingulate Cortex as a Key Driver of Mood Disorders in Gastrointestinal Disease and Disorders

“…Indeed, we review in subsequent sections data showing that some changes are neurochemical (that are likely reversed quickly), whereas others are involve extensive restructuring of neural morphology (which cannot be undone quickly/easily). Moreover, GIDD are risk factors for several age-related neurodegenerative diseases, including Parkinson's (65)(66)(67) and Alzheimer's (68). It is therefore possible that GIDD evokes brain changes that are less reversible in elderly people, as a consequence of the additive effects of inflammaging (69).…”

Gut–Brain Axis: Potential Factors Involved in the Pathogenesis of Parkinson's Disease

“…Rotenone has been reported to inhibit mitochondrial complex 1 activity, whereas paraquat causes oxidative stress (55)(56)(57)(58). The gramnegative bacteria endotoxin lipopolysaccharides (LPS) have also been reported to induce dopaminergic neuron death in animal models (59)(60)(61). Supporting Braak's theory of a peripheral-tocentral spread, agrochemicals such as metals, pesticides, and herbicides that enter the body via inhalation and/or ingestion are suggested to be a possible initiator causing widespread inflammation and mitochondrial dysfunction which ultimately lead to abnormal α-syn accumulation and dopaminergic neuron degeneration in the midbrain (10,59,62).…”