... Abstract Orexins have received a lot of attention as potent endogenous arousal-promoting peptides, and orexin receptor antagonists have shown clinical efficacy for the treatment of insomnia. Orexin neurons are thought to act primarily on monoaminergic neurons to maintain arousal and vigilance...

... Abstract The hypocretins/orexins are two excitatory neuropeptides, alternately called HCRT1 or orexin-A and HCRT2 or orexin-B, that are the endogenous ligands for two G-protein-coupled receptors, HCRTR1/OX 1 R and HCRTR2/OX 2 R. Shortly after the discovery of this system, degeneration...

... Abstract Orexins regulate a wide variety of biological functions, most notably the sleep-wake cycle, reward and stress processing, alertness, vigilance, and cognitive functioning. Alterations of central and peripheral orexin levels are linked to conditions such as narcolepsy, anorexia nervosa...

... Abstract Hypothalamic hypocretin/orexin neurons have been initially conceptualized as slow, modulatory controllers of behavior. Furthermore, their behavioral effects have been assumed to be a secondary consequence of their impact on arousal. However, cellular-resolution calcium imaging...

... Abstract The multifunctional, hypothalamic hypocretin/orexin (HCRT)-producing neurons regulate an array of physiological and behavioral states including arousal, sleep, feeding, emotions, stress, and reward. How a presumably uniform HCRT neuron population regulates such a diverse set...

... Abstract Orexin receptors (OXRs) are promiscuous G-protein-coupled receptors that signal via several G-proteins and, putatively, via other proteins. On which basis the signal pathways are selected and orchestrated is largely unknown. We also have an insufficient understanding of the kind...

... Abstract Since its description in the 19th century, narcolepsy type 1 (NT1) has been considered as a model sleep disorder, and after the discovery of rapid eye movement (REM) sleep onset in the disorder, a gateway to understanding REM sleep. The discovery that NT1 is caused by hypocretin/orexin...

... Abstract Significant sleep impairments often accompany substance use disorders (SUDs). Sleep disturbances in SUD patients are associated with poor clinical outcomes and treatment adherence, emphasizing the importance of normalizing sleep when treating SUDs. Orexins (hypocretins...

... due to sleep disturbance at night, consistent with a diagnosis of insomnia disorder. The hypothalamic neuropeptides, orexin-A and orexin-B, act through G-protein-coupled receptors (orexin-1 and orexin-2 receptors). Dual and selective orexin-2 receptor antagonists have shown efficacy in inducing sleep...

... such as Alzheimer’s disease (AD), and vice versa. New theories on the link between sleep and β-amyloid and tau secretion, accumulation and clearance, and its interaction with hypocretins/orexins (key neuropeptides regulating wakefulness) suggest mechanistic ways to better understand the impact of sleep alterations...

... Orexins (hypocretins) and their receptors were discovered in 1998. Orexin neuropeptides are produced by a very small number of cells in the lateral hypothalamus, suggesting a fundamental role in homeostasis. Despite the name “orexin,” which was coined after the original discovery of its role...

... al: Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 1998;92:573–585. 3. Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, et al: Narcolepsy in orexin knockout mice: molecular genetics...

...References References 1. Kukkonen JP: Recent progress in orexin/hypocretin physiology and pharmacology. Biomol Concepts 2012;3:447–463. 2. Kukkonen JP: Physiology of the orexinergic/hypocretinergic system: a revisit in 2012. Am J Physiol Cell Physiol 2013;301:C2–C32. 3. Kukkonen JP...

...References References 1. Sakurai T: The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci 2007;8:171–181. 2. Nishino S, Ripley B, Overeem S, Lammers GJ, Mignot E: Hypocretin (orexin) deficiency in human narcolepsy. Lancet 2000;355:39–40. 3...

...References References 1. Li Y, Gao XB, Sakurai T, van den Pol AN: Hypocretin/Orexin excites hypocretin neurons via a local glutamate neuron-A potential mechanism for orchestrating the hypothalamic arousal system. Neuron 2002;36:1169–1181. 2. Burdakov D: Electrical signaling in central...

...:657–659. 9. James MH, Mahler SV, Moorman DE, Aston-Jones G: A decade of orexin/hypocretin and addiction: where are we now? Curr Top Behav Neurosci 2017;33:247–281. 10. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, et al: Orexins and orexin receptors: a family...

...References References 1. Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, et al: Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 1999;98:437–451. 2. Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, et al: The sleep disorder canine...

...References References 1. Simerly RB. Chapter 13 – Organization of the Hypothalamus; in Paxinos G (ed): The Rat Nervous System, ed 4. San Diego, Academic Press, 2015, pp 267–294. 2. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, et al: Orexins and orexin receptors...

... al: Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 1998;92:573–585. 3. Gautvik KM, de Lecea L, Gautvik VT, Danielson PE, Tranque P, Dopazo A, et al: Overview of the most prevalent hypothalamus-specific...