Munteanu Constantin, Galaction Anca Irina, Turnea Marius, Blendea Corneliu Dan, Rotariu Mariana, Poștaru Mădălina
Department of Biomedical Sciences, Faculty of Medical Bioengineering, University of Medicine and Pharmacy "Grigore T. Popa" Iasi, 700115 Iasi, Romania.
Neuromuscular Rehabilitation Clinic Division, Clinical Emergency Hospital "Bagdasar-Arseni", 041915 Bucharest, Romania.
Antioxidants (Basel). 2024 Aug 30;13(9):1062. doi: 10.3390/antiox13091062.
Neurodegenerative diseases encompass a spectrum of disorders marked by the progressive degeneration of the structure and function of the nervous system. These conditions, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS), often lead to severe cognitive and motor deficits. A critical component of neurodegenerative disease pathologies is the imbalance between pro-oxidant and antioxidant mechanisms, culminating in oxidative stress. The brain's high oxygen consumption and lipid-rich environment make it particularly vulnerable to oxidative damage. Pro-oxidants such as reactive nitrogen species (RNS) and reactive oxygen species (ROS) are continuously generated during normal metabolism, counteracted by enzymatic and non-enzymatic antioxidant defenses. In neurodegenerative diseases, this balance is disrupted, leading to neuronal damage. This systematic review explores the roles of oxidative stress, gut microbiota, and epigenetic modifications in neurodegenerative diseases, aiming to elucidate the interplay between these factors and identify potential therapeutic strategies. We conducted a comprehensive search of articles published in 2024 across major databases, focusing on studies examining the relationships between redox homeostasis, gut microbiota, and epigenetic changes in neurodegeneration. A total of 161 studies were included, comprising clinical trials, observational studies, and experimental research. Our findings reveal that oxidative stress plays a central role in the pathogenesis of neurodegenerative diseases, with gut microbiota composition and epigenetic modifications significantly influencing redox balance. Specific bacterial taxa and epigenetic markers were identified as potential modulators of oxidative stress, suggesting novel avenues for therapeutic intervention. Moreover, recent evidence from human and animal studies supports the emerging concept of targeting redox homeostasis through microbiota and epigenetic therapies. Future research should focus on validating these targets in clinical settings and exploring the potential for personalized medicine strategies based on individual microbiota and epigenetic profiles.
神经退行性疾病涵盖一系列以神经系统结构和功能进行性退化为特征的病症。这些疾病，包括帕金森病（PD）、阿尔茨海默病（AD）、亨廷顿舞蹈病（HD）、肌萎缩侧索硬化症（ALS）和多发性硬化症（MS），常常导致严重的认知和运动功能障碍。神经退行性疾病病理的一个关键组成部分是促氧化剂和抗氧化剂机制之间的失衡，最终导致氧化应激。大脑的高氧消耗和富含脂质的环境使其特别容易受到氧化损伤。诸如活性氮物质（RNS）和活性氧物质（ROS）等促氧化剂在正常代谢过程中持续产生，由酶促和非酶促抗氧化防御机制进行抵消。在神经退行性疾病中，这种平衡被打破，导致神经元损伤。本系统综述探讨氧化应激、肠道微生物群和表观遗传修饰在神经退行性疾病中的作用，旨在阐明这些因素之间的相互作用，并确定潜在的治疗策略。我们对2024年在各大数据库发表的文章进行了全面检索，重点关注研究神经退行性变中氧化还原稳态、肠道微生物群和表观遗传变化之间关系的研究。共纳入161项研究，包括临床试验、观察性研究和实验性研究。我们的研究结果表明，氧化应激在神经退行性疾病的发病机制中起核心作用，肠道微生物群组成和表观遗传修饰显著影响氧化还原平衡。特定的细菌分类群和表观遗传标记被确定为氧化应激的潜在调节因子，为治疗干预提供了新的途径。此外，来自人类和动物研究的最新证据支持通过微生物群和表观遗传疗法靶向氧化还原稳态这一新兴概念。未来的研究应侧重于在临床环境中验证这些靶点，并探索基于个体微生物群和表观遗传特征的个性化医疗策略的潜力。
