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. 2022 May;162(6):1574-1582.
doi: 10.1053/j.gastro.2022.02.004. Epub 2022 Feb 8.

2021 Workshop: Neurodegenerative Diseases in the Gut-Brain Axis-Parkinson's Disease

Gary M Mawe  1 , Kirsteen N Browning  2 , Fredric P Manfredsson  3 , Michael Camilleri  4 , Frank A Hamilton  5 , Jonathan A Hollander  6 , Beth-Anne Sieber  7 , Patricia Greenwel  5 , Terez Shea-Donohue  5 , John W Wiley  8
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2021 Workshop: Neurodegenerative Diseases in the Gut-Brain Axis-Parkinson's Disease

Gary M Mawe et al. Gastroenterology. 2022 May.
No abstract available

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Figures

Figure 1.
Figure 1.
Schematic diagram summarizing potential mechanisms contributing that underlie gastrointestinal dyfunctions associated with Parkinson’s Disease and related links between the gut and the brain. The integrity of the mucosal barrier is maintained by specific contribution from the lining epithelial cells including enteroendocrine cells (EEC), the enteric nervous system (ENS), and immune cells. Epithelial cells undergo constant renewal and are replenished by a stable population of stem cells at the base of the crypts. Aging and exposure to environmental toxins are risk factors for Parkinson’s disease and are associated with impaired mucosal barrier function. A "leaky" gut (1) facilitates entry of luminal microbes and their products as well as ingested toxins into the systemic circulation (2). This triggers activation of resident immune cells and inflammation (3) that disrupt enteric neuronal and glial function (4) that can lead to induction of α-SYN misfolding within enteric neurons and neurodegeneration (5). Misfolded α-SYN may be transferred to the CNS via retrograde transport through the efferent vagus nerve resulting in aggregated α-SYN within brainstem vagal motoneurons (6). Misfolded α-SYN may also spread centrally in a prion like manner, including to the SNpc via the monosynaptic nigro-vagal pathway, causing reactive astrogliosis and loss of dopaminergic neurons resulting in the classic motor symptoms of PD (7). In this manner, age, environment, diet, and toxins may affect the induction, pathogenesis, and rate of disease progression at multiple peripheral and central sites of action. Abbreviations: α-SYN , alpha-synuclein; AP, area postrema; NTS, nucleus tractus solitarius; DMV, dorsal motor nucleus of the vagus; SNpc, substantial nigra pars compacta
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