Poltava State Medical University, Poltava 36000, Ukraine.
UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Malaysia.
Ageing Res Rev. 2022 Feb;74:101554. doi: 10.1016/j.arr.2021.101554. Epub 2021 Dec 30.
Parkinson's disease (PD) is a common motor disorder that has become increasingly prevalent in the ageing population. Recent works have suggested that circadian rhythms disruption is a common event in PD patients. Clock genes regulate the circadian rhythm of biological processes in eukaryotic organisms, but their roles in PD remain unclear. Despite this, several lines of evidence point to the possibility that clock genes may have a significant impact on the development and progression of the disease. This review aims to consolidate recent understanding of the roles of clock genes in PD. We first summarized the findings of clock gene expression and epigenetic analyses in PD patients and animal models. We also discussed the potential contributory role of clock gene variants in the development of PD and/or its symptoms. We further reviewed the mechanisms by which clock genes affect mitochondrial dynamics as well as the rhythmic synthesis and secretion of endocrine hormones, the impairment of which may contribute to the development of PD. Finally, we discussed the limitations of the currently available studies, and suggested future potential studies to deepen our understanding of the roles of clock genes in PD pathogenesis.
帕金森病(PD)是一种常见的运动障碍,在老年人群中发病率越来越高。最近的研究表明,生物钟紊乱是 PD 患者的常见事件。生物钟基因调节真核生物生物过程的昼夜节律,但它们在 PD 中的作用尚不清楚。尽管如此,有几条证据表明,生物钟基因可能对疾病的发展和进展有重大影响。本综述旨在综合最近关于时钟基因在 PD 中的作用的认识。我们首先总结了 PD 患者和动物模型中时钟基因表达和表观遗传分析的发现。我们还讨论了时钟基因变异在 PD 的发展和/或其症状中的潜在作用。我们进一步综述了时钟基因影响线粒体动力学以及内分泌激素节律性合成和分泌的机制,这些机制的损伤可能导致 PD 的发生。最后,我们讨论了目前可用研究的局限性,并提出了未来的潜在研究,以加深我们对时钟基因在 PD 发病机制中的作用的理解。