PDF(Pubmed)
Abstract：
BACKGROUND: Circadian rhythms (CRs) orchestrate intrinsic 24-hour oscillations which synchronize an organism\'s physiology and behaviour with respect to daily cycles. CR disruptions have been linked to Parkinson\'s Disease (PD), the second most prevalent neurodegenerative disorder globally, and are associated to several PD-symptoms such as sleep disturbances. Studying molecular changes of CR offers a potential avenue for unravelling novel insights into the PD progression, symptoms, and can be further used for optimization of treatment strategies. Yet, a comprehensive characterization of the alterations at the molecular expression level for core-clock and clock-controlled genes in PD is still missing.
METHODS: The proposed study protocol will be used to characterize expression profiles of circadian genes obtained from saliva samples in PD patients and controls. For this purpose, 20 healthy controls and 70 PD patients will be recruited. Data from clinical assessment, questionnaires, actigraphy tracking and polysomnography will be collected and clinical evaluations will be repeated as a follow-up in one-year time. We plan to carry out sub-group analyses considering several clinical factors (e.g., biological sex, treatment dosages, or fluctuation of symptoms), and to correlate reflected changes in CR of measured genes with distinct PD phenotypes (diffuse malignant and mild/motor-predominant). Additionally, using NanoStringⓇ multiplex technology on a subset of samples, we aim to further explore potential CR alterations in hundreds of genes involved in neuropathology pathways.
CONCLUSIONS: CLOCK4PD is a mono-centric, non-interventional observational study aiming at the molecular characterization of CR alterations in PD. We further plan to determine physiological modifications in sleep and activity patterns, and clinical factors correlating with the observed CR changes. Our study may provide valuable insights into the intricate interplay between CR and PD with a potential to be used as a predictor of circadian alterations reflecting distinct disease phenotypes, symptoms, and progression outcomes.
METHODS: The proposed study protocol will be used to characterize expression profiles of circadian genes obtained from saliva samples in PD patients and controls. For this purpose, 20 healthy controls and 70 PD patients will be recruited. Data from clinical assessment, questionnaires, actigraphy tracking and polysomnography will be collected and clinical evaluations will be repeated as a follow-up in one-year time. We plan to carry out sub-group analyses considering several clinical factors (e.g., biological sex, treatment dosages, or fluctuation of symptoms), and to correlate reflected changes in CR of measured genes with distinct PD phenotypes (diffuse malignant and mild/motor-predominant). Additionally, using NanoStringⓇ multiplex technology on a subset of samples, we aim to further explore potential CR alterations in hundreds of genes involved in neuropathology pathways.
CONCLUSIONS: CLOCK4PD is a mono-centric, non-interventional observational study aiming at the molecular characterization of CR alterations in PD. We further plan to determine physiological modifications in sleep and activity patterns, and clinical factors correlating with the observed CR changes. Our study may provide valuable insights into the intricate interplay between CR and PD with a potential to be used as a predictor of circadian alterations reflecting distinct disease phenotypes, symptoms, and progression outcomes.
摘要：
背景：昼夜节律（CR）协调内在的24小时振荡，使生物体的生理和行为与每日周期同步。CR中断与帕金森病（PD）有关，全球第二流行的神经退行性疾病，与睡眠障碍等多种PD症状有关。研究CR的分子变化为揭示PD进展的新见解提供了潜在的途径，症状,并可进一步用于治疗策略的优化。然而，PD中核心时钟和时钟控制基因在分子表达水平上的改变的综合特征仍然缺失.
方法：提出的研究方案将用于表征从PD患者和对照唾液样品中获得的昼夜节律基因的表达谱。为此,将招募20名健康对照和70名PD患者。来自临床评估的数据，问卷，将收集体动描记术和多导睡眠描记术,并在一年的时间内重复进行临床评估作为随访.我们计划考虑几个临床因素进行亚组分析(例如，生物性别，治疗剂量,或症状的波动)，并将测得的基因的CR变化与不同的PD表型（弥漫性恶性和轻度/运动优势）相关联。此外,在样本的一个子集上使用NanoString®多路复用技术，我们旨在进一步探索涉及神经病理学通路的数百个基因中潜在的CR改变.
结论：CLOCK4PD是单中心的，非干预性观察性研究旨在对PD中CR改变的分子特征进行研究。我们进一步计划确定睡眠和活动模式的生理变化，以及与观察到的CR变化相关的临床因素。我们的研究可能为CR和PD之间的复杂相互作用提供有价值的见解，并有可能用作反映不同疾病表型的昼夜节律变化的预测因子。症状,和进展结果。
方法：提出的研究方案将用于表征从PD患者和对照唾液样品中获得的昼夜节律基因的表达谱。为此,将招募20名健康对照和70名PD患者。来自临床评估的数据，问卷，将收集体动描记术和多导睡眠描记术,并在一年的时间内重复进行临床评估作为随访.我们计划考虑几个临床因素进行亚组分析(例如，生物性别，治疗剂量,或症状的波动)，并将测得的基因的CR变化与不同的PD表型（弥漫性恶性和轻度/运动优势）相关联。此外,在样本的一个子集上使用NanoString®多路复用技术，我们旨在进一步探索涉及神经病理学通路的数百个基因中潜在的CR改变.
结论：CLOCK4PD是单中心的，非干预性观察性研究旨在对PD中CR改变的分子特征进行研究。我们进一步计划确定睡眠和活动模式的生理变化，以及与观察到的CR变化相关的临床因素。我们的研究可能为CR和PD之间的复杂相互作用提供有价值的见解，并有可能用作反映不同疾病表型的昼夜节律变化的预测因子。症状,和进展结果。
