Chronic DSS-Induced Colitis Exacerbates Parkinson’s Disease Phenotype and Its Pathological Features Following Intragastric Rotenone Exposure
| Authors | |
|---|---|
| Year of publication | 2025 |
| Type | Article in Periodical |
| Magazine / Source | ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE |
| MU Faculty or unit | |
| Citation | |
| web | https://pubs.acs.org/doi/full/10.1021/acsptsci.4c00286 |
| Doi | http://dx.doi.org/10.1021/acsptsci.4c00286 |
| Keywords | Parkinson’s disease; gut inflammation; inflammatory bowel disease; ? synuclein; gut–brain axis |
| Description | Parkinson’s disease (PD) is not just reflective of synucleinopathies that affect the brain but also the gastrointestinal (GI) tract. (1) The pathological features of PD include the loss of dopaminergic (DAergic) neurons within substantia nigra pars compacta (SNpc), as well as the appearance of intraneuronal inclusions known as Lewy bodies or Lewy neurites, which are primarily composed of self-aggregatory protein ?-synuclein (?-syn). (2) Globally, an estimated 6.2 million people are believed to have PD and its prevalence is expected to increase 2.5-fold by 2040. (3) In addition, recent epidemiological research also suggests that PD patients have a variety of prodromal GI dysfunctions, including delayed gastric emptying, infrequent bowel movements, and chronic constipation, decades before they acquire centrally driven motor deficits of PD. (4) Correspondingly, GI tissue of PD patients has shown changes in functional and structural activities during the early stage of the disease, including the presence of ?-syn-containing inclusions, impaired mucosal barrier function, and altered bacterial composition. (5,6) The presentation of GI pathology is linked with the Braak hypothesis, which states that ingestion/inhalation of unknown environmental triggers causes the development of ?-syn pathology first in the enteric nervous system (ENS), followed by impacted lower brain stem regions, such as the dorsal motor nucleus of the vagus nerve (DMV), locus coeruleus (LC), and subsequently to the SNpc, where it induces death of DAergic neurons. (7) In support of this, several preclinical studies have recently demonstrated transneuronal transfer of injected recombinant ?-syn into the gut wall to the brain via the vagal nerve. (8-10) Clinical studies have also revealed that complete truncal vagotomy is now linked to a lower risk of PD. (11) These reports indicate that enteric ?-syn pathology can spread from the GI tract to the brain. Still, only a few studies have been conducted to explain the molecular mechanism associated with the development of enteric ?-syn pathology and its long-distance upward transmission to the brain. |
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