title: Hypocretin and its emerging role as a target for treatment of sleep disorders.
abstract: The neuropeptides hypocretin-1 and -2 (orexin A and B) are critical in the regulation of arousal and maintenance of wakefulness. Understanding the role of the hypocretin system in sleep/wake regulation has come from narcolepsy-cataplexy research. Deficiency of hypocretin results in loss of sleep/wake control with consequent unstable transitions from wakefulness into non-rapid eye movement (REM) and REM sleep, and clinical manifestations including daytime hypersomnolence, sleep attacks, and cataplexy. The hypocretin system regulates sleep/wake control through complex interactions between monoaminergic/cholinergic wake-promoting and GABAergic sleep-promoting neuronal systems. Research for the hypocretin agonist and the hypocretin antagonist for the treatment of sleep disorders has vigorously increased over the past 10 years. This review will focus on the origin, functions, and mechanisms in which the hypocretin system regulates sleep and wakefulness, and discuss its emerging role as a target for the treatment of sleep disorders.
authors.affiliation: Stanford University Sleep Medicine, 450 Broadway Street, Pavilion C, 2nd Floor, M/C 5704, Redwood City, CA 94063, USA. mhtcao1@stanford.edu
authors.forename: Michelle
authors.initials: M
authors.lastname: Cao
authors.forename: Christian
authors.initials: C
authors.lastname: Guilleminault
mesh_terms: D002385:Cataplexy / Q000503:physiopathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009290:Narcolepsy / Q000503:physiopathology; D009479:Neuropeptides / Q000378:metabolism*; D000068797:Orexins; D018013:Receptors, Neuropeptide / Q000378:metabolism; D012890:Sleep / Q000502:physiology; D012893:Sleep Wake Disorders / Q000188:drug therapy* / Q000503:physiopathology; D014851:Wakefulness / Q000502:physiology
chemical_list: C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D018013:Receptors, Neuropeptide