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http://hdl.handle.net/1942/43472
Title: | Genomic stress in diseases stemming from defects in the second brain | Authors: | MOMBEEK, Lobke BOESMANS, Werend WILSON, David |
Issue Date: | 2024 | Publisher: | WILEY | Source: | Neurogastroenterology and motility (Print), | Status: | Early view | Abstract: | This review discusses the less-explored realm of DNA damage and repair within the enteric nervous system (ENS), often referred to as the "second brain." While the central nervous system has been extensively studied for its DNA repair mechanisms and associated neuropathologies, the ENS, which can autonomously coordinate gastrointestinal function, experiences unique challenges and vulnerabilities related to its genome integrity. The susceptibility of the ENS to DNA damage is exacerbated by its limited protective barriers, resulting in not only endogenous genotoxic exposures, such as oxidative stress, but also exogenous threats, such as ingested environmental contaminants, local inflammatory responses, and gut dysbiosis. Here, we discuss the evidence for DNA repair defects in enteric neuropathies, most notably, the reported relationship between inherited mutations in RAD21 and LIG3 with chronic intestinal pseudo-obstruction and mitochondrial gastrointestinal encephalomyopathy disorders, respectively. We also introduce the lesser-recognized gastrointestinal complications in DNA repair syndromes, including conditions like Cockayne syndrome. The review concludes by pointing out the potential role of DNA repair defects in not only congenital disorders but also aging-related gut dysfunction, as well as the crucial need for further research to establish direct causal links between DNA damage accumulation and ENS-specific pathologic phenotypes. | Keywords: | DNA damage;DNA repair;enteric nervous system;enteric neuropathies;gastrointestinal motility;genomic instability | Document URI: | http://hdl.handle.net/1942/43472 | ISSN: | 1350-1925 | e-ISSN: | 1365-2982 | DOI: | 10.1111/nmo.14860 | ISI #: | 001267128300001 | Rights: | 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
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Genomic stress in diseases stemming from defects in the second brain.pdf | Early view | 3.05 MB | Adobe PDF | View/Open |
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