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.
摘要:
这篇综述讨论了肠神经系统(ENS)中DNA损伤和修复的探索较少的领域,通常被称为“第二大脑”。“虽然中枢神经系统的DNA修复机制和相关的神经病理学已经得到了广泛的研究,ENS,可以自主协调胃肠功能,经历了与其基因组完整性相关的独特挑战和脆弱性。ENS对DNA损伤的敏感性因其有限的保护屏障而加剧,不仅导致内源性基因毒性暴露,如氧化应激,但也有外来威胁,如摄入的环境污染物,局部炎症反应,和肠道生态失调。这里,我们讨论了肠神经病中DNA修复缺陷的证据,最值得注意的是,据报道,RAD21和LIG3的遗传突变与慢性肠假性梗阻和线粒体胃肠道脑肌病之间的关系,分别。我们还介绍了DNA修复综合征中较少认识的胃肠道并发症,包括像Cockayne综合征这样的病症.该综述最后指出了DNA修复缺陷不仅在先天性疾病中而且在与衰老相关的肠道功能障碍中的潜在作用。以及迫切需要进一步研究以建立DNA损伤积累与ENS特异性病理表型之间的直接因果关系。