The hypocretin/orexin system in sleep disorders: preclinical insights and clinical progress.
The hypocretin/orexin system in sleep disorders: preclinical insights and clinical progress.
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DOI：
10.2147/nss.s76711
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发表时间：
2016
影响因子：
3.4
通讯作者：
Cao M
中科院分区：
文献类型：
--
作者：
Chow M;Cao M
下丘脑分泌素/食欲素（HCRT/OX）系统在睡眠-觉醒调节中的作用主要来自于发作性睡病-惊厥的研究。下丘脑泌素-1和-2/食欲素-A和-B（分别为HCRT-1和-2/OX-A和-B）与觉醒的调节密切相关。HCRT/OX系统通过单胺能/胆碱能（促进觉醒）和γ-氨基丁酸能（促进睡眠）神经元系统之间的复杂相互作用来调节睡眠-觉醒控制。HCRT/OX的缺乏导致睡眠-觉醒控制或稳定性的丧失，从而导致觉醒到非快速眼动睡眠和快速眼动睡眠之间的不稳定过渡。这在临床上表现为异常的白天嗜睡，伴有睡眠发作和昏迷。随着美国食品和药物管理局批准首个用于治疗失眠的HCRT/OX双重受体拮抗剂，用于治疗睡眠障碍的HCRT/OX激动剂和拮抗剂的开发研究急剧增加。本文就HCRT/OX受体的起源、作用机制、临床研究进展及其在睡眠障碍治疗中的应用作一综述。
Much of the understanding of the hypocretin/orexin (HCRT/OX) system in sleep–wake regulation came from narcolepsy–cataplexy research. The neuropeptides hypocretin-1 and -2/orexin-A and -B (HCRT-1 and -2/OX-A and -B, respectively), as we know, are intimately involved in the regulation wakefulness. The HCRT/OX system regulates sleep–wake control through complex interactions between monoaminergic/cholinergic (wake-promoting) and gamma-aminobutyric acid-ergic (sleep-promoting) neuronal systems. Deficiency of HCRT/OX results in loss of sleep–wake control or stability with consequent unstable transitions between wakefulness to nonrapid eye movement and rapid eye movement sleep. This manifests clinically as abnormal daytime sleepiness with sleep attacks and cataplexy. Research on the development of HCRT/OX agonists and antagonists for the treatment of sleep disorders has dramatically increased with the US Food and Drug Administration approval of the first-in-class dual HCRT/OX receptor antagonist for the treatment of insomnia. This review focuses on the origin, mechanisms of HCRT/OX receptors, clinical progress, and applications for the treatment of sleep disorders.