Lu Yitong, Shang Ruirui, Zhong Xia, Shi Jingbo, Zhang Guangheng, Zhao Weijie, Teng Jing
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China.
College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
Front Pharmacol. 2025 Aug 29;16:1616322. doi: 10.3389/fphar.2025.1616322. eCollection 2025.
MDD is a complex mental illness shaped by the interplay between genetic vulnerability and environmental triggers. Its underlying pathophysiological processes are now understood to be influenced by epigenetic mechanisms. Growing evidence points to critical roles for DNA methylation, histone modification, and ncRNAs in driving transcriptional dysregulation within key brain regions implicated in MDD. These epigenetic alterations may underlie the persistent impairments in neuroplasticity following environmental stress exposure. NPs, renowned for their multi-target properties, have demonstrated promise in modulating epigenetic processes. However, a systematic synthesis of their regulatory roles, mechanisms, and therapeutic potential remains incomplete. This review aims to bridge this gap by integrating evidence from PubMed, Web of Science, and Embase databases to elucidate the role of epigenetic modifications in the pathogenesis and progression of MDD, dissect the mechanisms through which NPs exert antidepressant effects via epigenetic regulation, and highlight current research limitations while proposing strategies for translational applications in both preclinical and clinical settings.
重度抑郁症（MDD）是一种复杂的精神疾病，由遗传易感性和环境触发因素之间的相互作用所塑造。目前已知其潜在的病理生理过程受表观遗传机制影响。越来越多的证据表明，DNA甲基化、组蛋白修饰和非编码RNA（ncRNAs）在导致MDD相关关键脑区转录失调方面起着关键作用。这些表观遗传改变可能是环境应激暴露后神经可塑性持续受损的基础。纳米粒子（NPs）以其多靶点特性而闻名，已显示出在调节表观遗传过程方面的潜力。然而，对其调节作用、机制和治疗潜力的系统综合仍不完整。本综述旨在通过整合来自PubMed、科学网和Embase数据库的证据来弥合这一差距，阐明表观遗传修饰在MDD发病机制和进展中的作用，剖析纳米粒子通过表观遗传调控发挥抗抑郁作用的机制，并突出当前研究的局限性，同时提出在临床前和临床环境中进行转化应用的策略。
