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Orexin, also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone, is caused by a lack of orexin in the brain due to destruction of the cells that produce it. It exists in the forms of orexin-A and orexin-B.
Non-24-hour sleep–wake disorder is one of several chronic circadian rhythm sleep disorders (CRSDs). It is defined as a "chronic steady pattern comprising [...] daily delays in sleep onset and wake times in an individual living in a society". Symptoms result when the non-entrained (free-running) endogenous circadian rhythm drifts out of alignment with the light–dark cycle in nature. Although this sleep disorder is more common in blind people, affecting up to 70% of the totally blind, it can also affect sighted people. Non-24 may also be comorbid with bipolar disorder, depression, and traumatic brain injury. The American Academy of Sleep Medicine (AASM) has provided CRSD guidelines since 2007 with the latest update released in 2015.
Cataplexy is a sudden and transient episode of muscle weakness accompanied by full conscious awareness, typically triggered by emotions such as laughing, crying, or terror. Cataplexy affects approximately 20% of people who have narcolepsy, and is caused by an autoimmune destruction of hypothalamic neurons that produce the neuropeptide hypocretin, which regulates arousal and has a role in stabilization of the transition between wake and sleep states. Cataplexy without narcolepsy is rare and the cause is unknown.
The lateral hypothalamus (LH), also called the lateral hypothalamic area (LHA), contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system; this system of neurons mediates an array of cognitive and physical processes, such as promoting feeding behavior and arousal, reducing pain perception, and regulating body temperature, digestive functions, and blood pressure, among many others. Clinically significant disorders that involve dysfunctions of the orexinergic projection system include narcolepsy, motility disorders or functional gastrointestinal disorders involving visceral hypersensitivity, and eating disorders.
The International Classification of Sleep Disorders (ICSD) is "a primary diagnostic, epidemiological and coding resource for clinicians and researchers in the field of sleep and sleep medicine". The ICSD was produced by the American Academy of Sleep Medicine (AASM) in association with the European Sleep Research Society, the Japanese Society of Sleep Research, and the Latin American Sleep Society. The classification was developed as a revision and update of the Diagnostic Classification of Sleep and Arousal Disorders (DCSAD) that was produced by both the Association of Sleep Disorders Centers (ASDC) and the Association for the Psychophysiological Study of Sleep and was published in the journal Sleep in 1979. A second edition, called ICSD-2, was published by the AASM in 2005. The third edition, ICSD-3, was released by the AASM in 2014. A text revision of the third edition (ICSD-3-TR) was published in 2023 by the AASM.
The orexin receptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor that binds the neuropeptide orexin. There are two variants, OX1 and OX2, each encoded by a different gene (HCRTR1, HCRTR2).
Orexin receptor type 1 (Ox1R or OX1), also known as hypocretin receptor type 1 (HcrtR1), is a protein that in humans is encoded by the HCRTR1 gene.
Orexin receptor type 2 (Ox2R or OX2), also known as hypocretin receptor type 2 (HcrtR2), is a protein that in humans is encoded by the HCRTR2 gene.
Orexin-A, also known as hypocretin-1, is a naturally occurring neuropeptide and orexin isoform. The orexinergic nucleus in the lateral hypothalamus is the primary orexin projection system in the brain.
Narcolepsy is a chronic neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. Narcolepsy paired with cataplexy is evidenced to be an autoimmune disorder. These experiences of cataplexy can be brought on by strong emotions. Less commonly, there may be vivid hallucinations or an inability to move while falling asleep or waking up. People with narcolepsy tend to sleep about the same number of hours per day as people without, but the quality of sleep tends to be lessened.
Idiopathic hypersomnia(IH) is a neurological disorder which is characterized primarily by excessive sleep and excessive daytime sleepiness (EDS). The condition typically becomes evident in early adulthood and most patients diagnosed with IH will have had the disorder for many years prior to their diagnosis. As of August 2021, an FDA-approved medication exists for IH called Xywav, which is oral solution of calcium, magnesium, potassium, and sodium oxybates; in addition to several off-label treatments (primarily FDA-approved narcolepsy medications).
Suvorexant, sold under the brand name Belsomra, is an orexin antagonist medication which is used in the treatment of insomnia. It is indicated specifically for the treatment of insomnia characterized by difficulties with sleep onset and/or maintenance in adults. Suvorexant helps with falling asleep faster, sleeping longer, being awake less in the middle of the night, and having better quality of sleep. Its effectiveness is modest, and is similar to that of other orexin antagonists, but is lower than that of benzodiazepines and Z-drugs. Suvorexant is taken by mouth.
An orexin receptor antagonist, or orexin antagonist, is a drug that inhibits the effect of orexin by acting as a receptor antagonist of one (selective orexin receptor antagonist or SORA) or both (dual orexin receptor antagonis or DORA) of the orexin receptors, OX1 and OX2. Medical applications include treatment of sleep disorders such as insomnia.
Emmanuel Mignot is a sleep researcher and director of the Stanford Center for Sleep Sciences and Medicine, at Stanford University. Dr. Mignot is an authority on sleep research and medicine, and is mostly known for his work on narcolepsy. He is the Craig Reynolds Professor of Sleep Medicine at Stanford Medical School, Stanford University.
Thomas S. Kilduff is an American neuroscientist and the director of SRI International's Center for Neuroscience. He specializes in neurobiology related to sleep and wakefulness, and was involved in the discovery of hypocretin, a neuropeptide system that is highly involved in wakefulness regulation.
Lemborexant, sold under the brand name Dayvigo, is an orexin antagonist medication which is used in the treatment of insomnia. It is indicated specifically for the treatment of insomnia characterized by difficulties with sleep onset and/or maintenance in adults. The medication is taken by mouth.
Classification of sleep disorders comprises systems for classifying medical disorders associated with sleep. Systems have changed, increasingly using technological discoveries to advance the understanding of sleep and recognition of sleep disorders.
Randy J. Nelson is an American neuroscientist who holds the Hazel Ruby McQuain Chair for Neurological Research and the founding chair of the Department of Neuroscience at the West Virginia University School of Medicine. Much of his research has focused on the contribution of circadian and seasonal rhythms on physiology and behavior.
Danavorexton is a selective orexin 2 receptor agonist. It is a small-molecule compound and is administered intravenously. The compound was found to dose-dependently produce wakefulness to a similar degree as modafinil in a phase 1 clinical trial. As of March 2021, danavorexton is under development for the treatment of narcolepsy, idiopathic hypersomnia, and sleep apnea. It is related to another orexin receptor agonist, firazorexton (TAK-994), the development of which was discontinued for safety reasons in October 2021.
Masashi Yanagisawa is a Japanese-American molecular biologist and physician, famous for his discovery of the hormone endothelin and the neuropeptide orexin, the absence of which is the cause of narcolepsy. He is currently the Director of the International Institute for Integrative Sleep Medicine, University of Tsukuba, and an adjunct professor at the Department of Molecular Genetics, University of Texas Southwestern Medical Center.
References
- ↑ Goldman, Bruce. "Stanford scientists solve secret of nerve cells marking a form of schizophrenia". Stanford Medicine News Center.
- ↑ "Many not sleeping enough – or well enough – and that's a killer". www.cbsnews.com.
- ↑ Chen, Ingfei (October 23, 2007). "From Faithful Dogs and Difficult Fish, Insight Into Narcolepsy" – via NYTimes.com.
- ↑ Shibata, Mari. "Why overtired Japan is turning to office siestas". www.bbc.com.
- ↑ Davis, Suryatapa Bhattacharya and River (September 19, 2019). "Yes, You Can Sleep on the Job. Just Please Use the Nap Room" – via www.wsj.com.
- ↑ Otake, Tomoko (November 9, 2017). "Japan's buzzwords of 2017 cover everything from politics to poop". The Japan Times.
- ↑ "Stanford Profiles".
- 1 2 3 4 "西野 精治 | 著者ページ". 東洋経済オンライン.
- ↑ Lewis, Leo (November 21, 2019). "Misery of Japanese workplaces shows few signs of lifting". www.ft.com.
- 1 2 "Ultimate Sound Sleep | Sunmark Publishing, Inc".
- ↑ "Seiji Nishino « World Alliance Forum in San Francisco".
- 1 2 3 4 5 6 7 8 9 "Seiji Nishino's Profile | Stanford Profiles". profiles.stanford.edu. Retrieved 2021-06-19.