The hypocretin/orexin system in health and disease.
Using positional cloning in a canine model of narcolepsy and mouse gene knockouts, genes involved in the pathogenesis of narcolepsy in animals have been identified. Hypocretin/orexin ligand and hypocretin/orexin receptor genes are key to the pathogenesis of narcolepsy in animals. Mutations in hypocretin-related genes are rare in humans, but hypocretin-ligand deficiency is found in many cases. Hypocretins/orexins are novel hypothalamic neuropeptides involved in various hypothalamic mechanisms, such as energy homeostasis and neuroendocrine function. Hypocretin-deficient human narcolepsy appears to be a more complex condition than a simple sleep disorder, and it may serve as an important disease model for studying hypothalamic function in health and disease.
Nishino
Seiji
S
Center for Narcolepsy, Stanford University, School of Medicine, Psychiatry and Behavioral Sciences, Palo Alto, California 94304, USA.
D017668:Age of Onset; D000818:Animals; D001069:Appetite Regulation; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism* / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D001523:Mental Disorders / Q000378:metabolism; D009154:Mutation; D009290:Narcolepsy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009479:Neuropeptides / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D064446:Orexin Receptors; D000068797:Orexins; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D012893:Sleep Wake Disorders / Q000378:metabolism
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide