Yalçin Müge, Grande Valentina, Outeiro Tiago Fleming, Relόgio Angela
Institute for Systems Medicine and Faculty of Human Medicine, MSH Medical School Hamburg, Hamburg, Germany.
Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany.
NPJ Parkinsons Dis. 2025 Jul 14;11(1):213. doi: 10.1038/s41531-025-01009-9.
Parkinson's Disease (PD) is a prevalent neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. This leads to hallmark motor features that include bradykinesia, resting tremor, rigidity, and postural instability, alongside with a range of non-motor symptoms including sleep disturbances, mood disorders, and cognitive decline. As global life expectancy rises, the prevalence of PD is expected to continue to increase, highlighting the urgent need for effective therapeutic strategies. Despite tremendous advances in our understanding of disease-associated mechanisms, we still do not fully understand the aetiology of PD. Emerging evidence points to the circadian clock-a system that regulates physiological processes such as sleep-wake cycles and hormone release-as a critical factor in PD pathophysiology. Disruptions in circadian rhythms (CR) are common in PD patients and may exacerbate both motor and non-motor symptoms, potentially influencing the progression of neurodegeneration. This review examines the global impact of PD within the context of an aging population, delves into the molecular underpinnings of the disease, and explores the role of CR in PD. We summarize and discuss key reports on molecular links between PD and CR using unbiased systematic search strategies to cover a broad literature. Finally, we discuss the potential of chronotherapy, the alignment of treatment with the body's natural rhythms, as a personalized approach in PD management, aiming to improve treatment efficacy and patient quality of life. Understanding the interplay between circadian biology and PD could pave the way for innovative, personalized therapeutic strategies.
帕金森病（PD）是一种常见的神经退行性疾病，其特征是黑质中多巴胺能神经元逐渐丧失。这导致了标志性的运动特征，包括运动迟缓、静止性震颤、僵硬和姿势不稳，同时还伴有一系列非运动症状，如睡眠障碍、情绪障碍和认知衰退。随着全球预期寿命的增加，帕金森病的患病率预计将继续上升，这凸显了对有效治疗策略的迫切需求。尽管我们对疾病相关机制的理解取得了巨大进展，但我们仍未完全了解帕金森病的病因。新出现的证据表明，生物钟——一个调节睡眠-觉醒周期和激素释放等生理过程的系统——是帕金森病病理生理学中的一个关键因素。昼夜节律紊乱在帕金森病患者中很常见，可能会加重运动和非运动症状，潜在地影响神经退行性变的进展。本综述探讨了在老龄化人口背景下帕金森病的全球影响，深入研究了该疾病的分子基础，并探讨了昼夜节律在帕金森病中的作用。我们使用无偏系统搜索策略总结和讨论了关于帕金森病与昼夜节律之间分子联系的关键报告，以涵盖广泛的文献。最后，我们讨论了时间疗法（使治疗与身体自然节律相匹配）作为帕金森病管理中的一种个性化方法的潜力，旨在提高治疗效果和患者生活质量。了解昼夜生物学与帕金森病之间的相互作用可为创新的个性化治疗策略铺平道路。
