title: Hypocretin ligand deficiency in narcolepsy: recent basic and clinical insights.
abstract: Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. Both sporadic and familial forms exist in humans. Recently, the major pathophysiology of human narcolepsy was indicated, based on discovery, through animal study, of narcolepsy genes involved in the pathology of hypocretin/orexin ligand and its receptor. Hypocretin ligand deficiency is found in most patients with narcolepsy with cataplexy. This deficiency likely is the result of postnatal cell death of hypocretin neurons, and involvement of autoimmune mechanisms is suggested. Hypocretin deficiency also is found in symptomatic narcolepsy and excessive daytime sleepiness with neurologic conditions, including immune-mediated neurologic disorders. These findings have significant clinical relevance and promote understanding of hypocretin cell death mechanisms. Already, discoveries in humans have led to a new diagnostic test for narcolepsy. Currently, hypocretin replacement therapy has emerged as a promising therapeutic option, and experiments using gene therapy and cell transplantation are in progress.
authors.affiliation: Center for Narcolepsy, Stanford School of Medicine, Stanford University Sleep and Circadian Neurobiology Laboratory, 1201 Welch Road, MSLS, P213, Palo Alto, CA 94304, USA.
authors.forename: Cayde
authors.initials: C
authors.lastname: Ritchie
authors.forename: Masashi
authors.initials: M
authors.lastname: Okuro
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanbayashi
authors.forename: Seiji
authors.initials: S
authors.lastname: Nishino
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics; D009290:Narcolepsy / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000172:deficiency* / Q000235:genetics; D064446:Orexin Receptors; D000068797:Orexins; D011110:Polymorphism, Genetic; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D018013:Receptors, Neuropeptide / Q000235:genetics; D012890:Sleep / Q000235:genetics / Q000502:physiology*
chemical_list: D051401:Aquaporin 4; D007155:Immunologic Factors; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide