目的:睡眠障碍是帕金森病(PD)最常见的非运动症状,它们在其他α-突触病变中也经常被报道,如路易体痴呆(DLB)和多系统萎缩(MSA)。最近,食欲素系统已经涉及到基于显著环境设定点的唤醒控制,翻译动物模型的发现表明α-突触核蛋白病中睡眠问题的失调。然而,其在α-突触核蛋白病患者中的作用尚不清楚.因此,我们开始系统地审查,并批判性地评估,关于alpha-突触核蛋白病中食欲能系统与睡眠障碍关联的当代证据。在这次系统审查中,研究α-突触核蛋白病中的食欲素和睡眠(快速眼动(REM)行为障碍(RBD),帕金森病(PD),路易体痴呆(DLB),多系统萎缩(MSA))使用PubMed的电子数据库搜索进行识别,WebofScienceandPsychINFO使用MeSH术语,关键词,以及诸如“α-突触核蛋白病”和“Orexin”和“睡眠障碍”之类的标题词。
结果:本系统综述纳入了17项研究,其中2项关于RBD的研究,10号在PD上,4在DLB上,MSA患者为1。一起来看,RBD和PD研究表明,在神经退行性过程的早期阶段,食欲素水平有潜在的适应性增加,降低的水平更经常被报告给以后,疾病的更晚期。迄今为止,MSA患者和健康对照组之间的食欲素水平没有差异。关于食欲素水平在α-突触核蛋白病中的作用的研究缺乏。此外,在当前工作中存在重大的方法学局限性,包括使用非标准化的研究方案和缺乏前瞻性,多中心研究,不允许任何关于潜在病理机制的有限结论。尽管如此,一张复杂的照片,在α-突触核蛋白病中,食欲能通路失调与睡眠障碍之间的多方面关系正在出现。因此,未来的研究迫切需要解开α-突触核蛋白病变的奥氧激能病理机制,以更全面地说明奥氧激能通路在α-突触核蛋白病变中的作用.食欲素的药理学操作可能在治疗策略中具有多种治疗应用,疾病诊断,并可能有效治疗运动和非运动症状。
OBJECTIVE: Sleep disturbances are amongst most frequent non-motor symptoms of Parkinson\'s Disease (PD), and they are similarly frequently reported in other alpha-syncleinopathies, such as Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA). More recently, the
orexin system has been implicated in control of arousal based on salient environmental set points, and its dysregulation in sleep issues in alpha-synucleinopathies suggested by the findings from the translational animal models. However, its role in the patients with alpha-synucleinopathies remains unclear. We thus set to systematically
review, and to critically assess, contemporary evidence on the association of the orexinergic system and sleep disturbances in alpha-synucleinopathies. In this systematic
review, studies investigating
orexin and sleep in alpha-synucleinopathies (Rapid Eye Movement (REM) Behaviour Disorder (RBD), Parkinson\'s Disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA)) were identified using electronic database searches of PubMed, Web of Science and PsychINFO using MeSH terms, keywords, and title words such as \"Alpha-synucleinopathies\" AND \"Orexin\" AND \"Sleep Disturbances\".
RESULTS: 17 studies were included in this systemic
review, of which 2 studies on RBD, 10 on PD, 4 on DLB, and 1 on MSA patients. Taken together, RBD and PD studies suggest a potential adaptive increase in orexin levels in early stages of the neurodegenerative process, with reduced levels more often reported for later, more advanced stages of illness. To date, no differences in orexin levels were demonstrated between MSA patients and healthy controls. There is a dearth of studies on the role of
orexin levels in alpha-synucleinopathies. Moreover, significant methodologic limitations in the current body of work, including use of non-standardised research protocols and lack of prospective, multi-centre studies, disallow for any finite conclusion in regards to underlying pathomechanisms. Nonetheless, a picture of a complex, multifaceted relationship between the dysregulation of the orexinergic pathway and sleep disturbances in alpha-synucleinopathies is emerging. Hence, future studies disentangling orexinergic pathomechanisms of alpha-syncleinopathies are urgently needed to obtain a more comprehensive account of the role of orexinergic pathway in alpha-synucleinopathies. Pharmacological manipulations of orexins may have multiple therapeutic applications in treatment strategies, disease diagnosis, and might be effective for treating both motor and non-motor symptoms.