昼夜节律紊乱在帕金森病睡眠障碍中的机制研究进展

Research Progress on Mechanisms of Circadian Rhythm Disruption in Sleep Disorders of Parkinson’s Disease

摘要: 帕金森病(Parkinson’s disease, PD)睡眠障碍患病率高，与α-突触核蛋白(α-syn)病理形成恶性循环。近年证据表明，昼夜节律紊乱是PD睡眠障碍的核心病理基础。本文系统梳理PD睡眠障碍相关的昼夜节律紊乱，从临床特征(静息–活动节律碎片化、核心体温与褪黑素及皮质醇节律异常)、分子机制(Bmal1/Clock等核心时钟基因表达异常及多巴胺能神经元节律调控)、双向病理关系(节律紊乱促进α-syn聚集，α-syn沉积损伤视交叉上核及节律脑区)以及神经环路基础(SCN-下丘脑–脑干睡眠–觉醒网络)四个层面进行整合分析，归纳出时钟基因/SCN功能退化、神经内分泌节律紊乱与节律-α-syn正反馈循环相互叠加的机制框架，并展望了时间疗法在PD睡眠障碍管理中的潜在应用价值。

Abstract: Sleep disorders are highly prevalent in Parkinson’s disease (PD) and form a vicious cycle with α-synuclein (α-syn) pathology. Emerging evidence indicates that circadian rhythm disruption is a core pathological basis of PD-related sleep disturbances. This review systematically examines circadian rhythm abnormalities associated with sleep disorders in PD, integrating evidence from four levels: clinical features (fragmentation of rest-activity rhythms, abnormalities in core body temperature, melatonin, and cortisol rhythms); molecular mechanisms (dysregulation of core clock genes such as Bmal1/Clock and their modulation of dopaminergic neuron rhythmicity); bidirectional pathological interactions (circadian disruption promoting α-syn aggregation, and α-syn deposition damaging the suprachiasmatic nucleus and other circadian brain regions); and neural circuit basis (the SCN-hypothalamus-brainstem sleep-wake network). Based on these findings, we propose an integrative framework in which clock gene/SCN dysfunction, neuroendocrine rhythm disruption, and a positive feedback loop between circadian dysregulation and α-syn pathology mutually reinforce each other. Finally, we discuss the potential application of chronotherapy in the management of sleep disorders in PD.