Teng Sisi, Han Cunqiao, Zhou Jian, He Zhenyan, Qian Weiwei
Department of Neurology, Shangjinnanfu Hospital, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Emergency, Shangjinnanfu Hospital, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Front Cell Dev Biol. 2024 Aug 8;12:1440143. doi: 10.3389/fcell.2024.1440143. eCollection 2024.
Alzheimer's disease (AD) is a neurodegenerative disorder caused by a variety of factors, including age, genetic susceptibility, cardiovascular disease, traumatic brain injury, and environmental factors. The pathogenesis of AD is largely associated with the overproduction and accumulation of amyloid-β peptides and the hyperphosphorylation of tau protein in the brain. Recent studies have identified the presence of diverse pathogens, including viruses, bacteria, and parasites, in the tissues of AD patients, underscoring the critical role of central nervous system infections in inducing pathological changes associated with AD. Nevertheless, it remains unestablished about the specific mechanism by which infections lead to the occurrence of AD. As an important post-transcriptional RNA modification, RNA 5-methylcytosine (mC) methylation regulates a wide range of biological processes, including RNA splicing, nuclear export, stability, and translation, therefore affecting cellular function. Moreover, it has been recently demonstrated that multiple pathogenic microbial infections are associated with the mC methylation of the host. However, the role of mC methylation in infectious AD is still uncertain. Therefore, this review discusses the mechanisms of pathogen-induced AD and summarizes research on the molecular mechanisms of mC methylation in infectious AD, thereby providing new insight into exploring the mechanism underlying infectious AD.
阿尔茨海默病(AD)是一种由多种因素引起的神经退行性疾病,这些因素包括年龄、遗传易感性、心血管疾病、创伤性脑损伤和环境因素。AD的发病机制在很大程度上与大脑中β-淀粉样肽的过度产生和积累以及tau蛋白的过度磷酸化有关。最近的研究已经在AD患者的组织中发现了多种病原体的存在,包括病毒、细菌和寄生虫,这突出了中枢神经系统感染在诱导与AD相关的病理变化中的关键作用。然而,感染导致AD发生的具体机制仍未明确。作为一种重要的转录后RNA修饰,RNA 5-甲基胞嘧啶(mC)甲基化调节广泛的生物学过程,包括RNA剪接、核输出、稳定性和翻译,从而影响细胞功能。此外,最近已经证明多种病原微生物感染与宿主的mC甲基化有关。然而,mC甲基化在感染性AD中的作用仍然不确定。因此,本综述讨论了病原体诱导AD的机制,并总结了感染性AD中mC甲基化分子机制的研究,从而为探索感染性AD的潜在机制提供了新的见解。