Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy and Joint Research Institution of Altitude Health and National Clinical Research Center for Geriatrics，West China Hospital, Sichuan University, Sichuan, Chengdu, China.
Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Med Res Rev. 2023 Sep;43(5):1748-1777. doi: 10.1002/med.21962. Epub 2023 Apr 29.
Parkinson's disease (PD) is a multifactorial disease due to a complex interplay between genetic and epigenetic factors. Recent efforts shed new light on the epigenetic mechanisms involved in regulating pathways related to the development of PD, including DNA methylation, posttranslational modifications of histones, and the presence of microRNA (miRNA or miR). Epigenetic regulators are potential therapeutic targets for neurodegenerative disorders. In the review, we aim to summarize mechanisms of epigenetic regulation in PD, and describe how the DNA methyltransferases, histone deacetylases, and histone acetyltransferases that mediate the key processes of PD are attractive therapeutic targets. We discuss the use of inhibitors and/or activators of these regulators in PD models or patients, and how these small molecule epigenetic modulators elicit neuroprotective effects. Further more, given the importance of miRNAs in PD, their contributions to the underlying mechanisms of PD will be discussed as well, together with miRNA-based therapies.
帕金森病（PD）是一种多因素疾病，是由于遗传和表观遗传因素之间的复杂相互作用所致。最近的研究工作揭示了参与调节与 PD 发生相关的途径的表观遗传机制，包括 DNA 甲基化、组蛋白翻译后修饰和 microRNA（miRNA 或 miR）的存在。表观遗传调节剂是神经退行性疾病的潜在治疗靶点。在综述中，我们旨在总结 PD 中表观遗传调控的机制，并描述介导 PD 关键过程的 DNA 甲基转移酶、组蛋白去乙酰化酶和组蛋白乙酰转移酶如何成为有吸引力的治疗靶点。我们讨论了在 PD 模型或患者中使用这些调节剂的抑制剂和/或激活剂，以及这些小分子表观遗传调节剂如何产生神经保护作用。此外，鉴于 miRNAs 在 PD 中的重要性，还将讨论它们对 PD 潜在机制的贡献，以及基于 miRNA 的治疗方法。
