Orexins
Orexin (), also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. It exists in the forms of orexin-A and orexin-B. The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone ("drop attacks" or cataplexy), is caused by a lack of orexin in the brain due to destruction of the cells that produce it.Stanford Center for NarcolepsFAQ(retrieved 27-Mar-2012) There are 50,000–80,000 orexin-producing neurons in the human brain, located predominantly in the perifornical area and lateral hypothalamus. They project widely throughout the central nervous system, regulating wakefulness, feeding, and other behaviours. There are two types of orexin peptide and two types of orexin receptor. Orexin was discovered in 1998 almost simultaneously by two independent groups of researchers working on the rat brain. One group named it orexin, from ''orexis,'' meaning "appetite" in Greek; the other group named it hy ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Orexin-B
Orexin (), also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. It exists in the forms of orexin-A and orexin-B. The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone ("drop attacks" or cataplexy), is caused by a lack of orexin in the brain due to destruction of the cells that produce it.Stanford Center for NarcolepsFAQ(retrieved 27-Mar-2012) There are 50,000–80,000 orexin-producing neurons in the human brain, located predominantly in the perifornical area and lateral hypothalamus. They project widely throughout the central nervous system, regulating wakefulness, feeding, and other behaviours. There are two types of orexin peptide and two types of orexin receptor (biochemistry), receptor. Orexin was discovered in 1998 almost simultaneously by two independent groups of researchers working on the laboratory rat, rat brain. One group named it orexin, from ''orexis,'' meaning "appetite" ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Narcolepsy
Narcolepsy is a chronic neurological disorder that impairs the ability to regulate sleep–wake cycles, and specifically impacts REM (rapid eye movement) sleep. The symptoms of narcolepsy include excessive daytime sleepiness (EDS), sleep-related hallucinations, sleep paralysis, disturbed nocturnal sleep (DNS), and cataplexy. People with narcolepsy typically have poor quality of sleep. There are two recognized forms of narcolepsy, narcolepsy type 1 and type 2. Narcolepsy type 1 (NT1) can be clinically characterized by symptoms of EDS and cataplexy, and/or will have cerebrospinal fluid (CSF) orexin levels of less than 110 pg/ml. Cataplexy are transient episodes of aberrant tone, most typically loss of tone, that can be associated with strong emotion. In pediatric-onset narcolepsy, active motor phenomena are not uncommon. Cataplexy may be mistaken for syncope, tics, or seizures. Narcolepsy type 2 (NT2) does not have features of cataplexy, and CSF orexin levels are normal. ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Lateral Hypothalamus
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 (e.g., irritable bowel syndrome), and eating disorders. The neurotransmitter glutamate and the endocannabinoids (e.g., anandamide) and the orexin neuropeptides orexin-A and orexin-B are the primary signaling neurochemicals in orexin neurons; pathway-specific neurochemicals include GABA, melanin-concentrating hormone, nociceptin, gluc ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Wakefulness
Wakefulness is a daily recurring brain state and state of consciousness in which an individual is conscious and engages in coherent cognition, cognitive and behavioral responses to the external world. Being awake is the opposite of being asleep, in which most external inputs to the brain are excluded from neural processing. Effects upon the brain The longer the brain has been awake, the greater the synchronous firing rates of cerebral cortex neurons. After sustained periods of sleep, both the speed and synchronicity of the neurons firing are shown to decrease. Another effect of wakefulness is the reduction of glycogen held in the astrocytes, which supply energy to the neurons. Studies have shown that one of sleep's underlying functions is to replenish this glycogen energy source. Maintenance by the brain Wakefulness is produced by a complex interaction between multiple neurotransmitter systems arising in the brainstem and ascending through the midbrain, hypothalamus, thalamus ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Orexin-A
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. Structure Orexin-A is a peptide composed of 33 amino acids including an N-terminal pyroglutamyl residue and two intramolecular disulfide bridges between cysteine residues in 6 and 12 and 7 and 14 positions. The amino acid sequence is: Pyroglu-Pro-Leu-Pro-Asp-Cys-Cys-Arg-Gln-Lys-Thr-Cys-Ser-Cys-Arg-Leu-Tyr-Glu-Leu-Leu-His-Gly-Ala-Gly-Asn-His-Ala-Ala-Gly-Ile-Leu-Thr-Leu. Mechanism Orexins are highly excitatory neuropeptides that were first discovered in the brains of rats. It is a peptide that is produced by a very small population of cells in the lateral and posterior hypothalamus. Orexins strongly excite various brain nuclei (neurons) to affect an organism's wakefulness by affecting their dopamine, norepinephrine, histamine and acetylcholine systems. These systems work together ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Orexin Receptor Type 1
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. Function The orexin 1 receptor (OX1), is a G-protein coupled receptor that is heavily expressed in projections from the lateral hypothalamus and is involved in the regulation of feeding behaviour. OX1 selectively binds the orexin-A neuropeptide. It shares 64% identity with OX2. Ligands Agonists * Orexin-A Antagonists * RTIOX-276 - Selective OX1 antagonist * ACT-335827 - Selective OX1 antagonist * Almorexant - Dual OX1 and OX2 antagonist * Lemborexant - Dual OX1 and OX2 antagonist * Nemorexant - Dual OX1 and OX2 antagonist * SB-334,867 - Selective OX1 antagonist * SB-408,124 - Selective OX1 antagonist * SB-649,868 - Dual OX1 and OX2 antagonist * Suvorexant - Dual OX1 and OX2 antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Incretin
Incretins are a group of metabolic hormones that decrease Blood sugar level, blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from Pancreas, pancreatic beta cells of the islets of Langerhans by a blood glucose, blood-glucose–dependent mechanism. Some incretins (GLP-1) also inhibit glucagon release from the alpha cells of the islets of Langerhans. In addition, they slow the rate of absorption of nutrients into the bloodstream by reducing Gastrointestinal physiology, gastric emptying and may reduce food intake. The two main peptides that fulfill criteria for an incretin are the intestinal peptide glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP, also known as: glucose-dependent insulinotropic polypeptide). GIP is produced and secreted into the blood by Enteroendocrine cell#K cell, K cells located in the mucosa of the upper gastrointestinal tract's duodenum and upper jejunum while GLP1 is produced and secrete ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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University Of Texas Southwestern Medical Center At Dallas
The University of Texas Southwestern Medical Center (UT Southwestern or UTSW) is a public academic health science center in Dallas, Texas. With approximately 23,000 employees, more than 3,000 full-time faculty, and nearly 4 million outpatient visits per year, UT Southwestern is the largest medical school in the University of Texas System and the State of Texas. UT Southwestern's operating budget in 2021 was more than , and is the largest medical institution in the Dallas–Fort Worth Metroplex (and therefore North Texas region), annually training about 3,800 medical, graduate, and health professions students, residents, and postdoctoral fellows. UT Southwestern Research Programs amounted to in 2022. UT Southwestern's faculty also provide services at Scottish Rite for Children, VA North Texas Health Care System, and other affiliated hospitals and community clinics in the North Texas region. Faculty and residents provide care in more than 80 specialties to more than 100,000 ho ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Orexin Receptor Type 2
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. It should not be confused for the protein CD200R1 which shares the alias OX2R but is a distinct, unrelated gene located on the human chromosome 3. Structure The structure of the receptor has been solved to 2.5 Å resolution as a fusion protein bound to suvorexant using lipid-mediated crystallization. Function OX2 is a G-protein coupled receptor expressed exclusively in the brain. It has 64% identity with Hypocretin (orexin) receptor 1, OX1. OX2 binds both orexin A and orexin B neuropeptides. OX2 is involved in the central feedback mechanism that regulates feeding behaviour. Mice with enhanced OX2 signaling are resistant to high-fat diet-induced obesity. This receptor is activated by Hipocretin, which is a wake-promoting hypothalamic neuropeptide that acts as a critical regulator of sleep in animals as Zebrafish or Mammal, M ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Scripps Research Institute
Scripps Research is a nonprofit American medical research facility that focuses on research and education in the biomedical sciences. Headquartered in San Diego, California, the institute has over 170 laboratories employing 2,100 scientists, technicians, graduate students, and administrative and other staff. The institute holds over 1,100 patents, has produced 11 FDA-approved therapeutics, and has generated over 50 spin-off companies. The Scripps Research graduate program is ranked 9th nationally in the biological sciences, 6th for organic chemistry, and 6th for biochemistry. In 2022, their Jupiter, Florida, campus became a part of the University of Florida. Jupiter-based graduate students remain part of the Scripps Research graduate program. History Scripps Research began with the Scripps Metabolic Clinic, founded near the current site in the La Jolla area of San Diego in 1924 by philanthropist Ellen Browning Scripps, who was inspired by the discovery of insulin. In 1946, the ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Neuropeptide
Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the gut, muscles, and heart. Neuropeptides are synthesized from large precursor proteins which are cleaved and post-translationally processed then packaged into large dense core vesicles. Neuropeptides are often co-released with other neuropeptides and neurotransmitters in a single neuron, yielding a multitude of effects. Once released, neuropeptides can diffuse widely to affect a broad range of targets. Neuropeptides are extremely ancient and highly diverse chemical messengers. Placozoa, Placozoans such as ''Trichoplax'', extremely basal animals which do not possess neurons, use peptides for cell-to-cell communication in a way similar to the neuropeptides of higher animals. Examples Peptide signals play a role in information processing t ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Limbic System
The limbic system, also known as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.Schacter, Daniel L. 2012. ''Psychology''.sec. 3.20 Its various components support a variety of functions including emotion, behavior, long-term memory, and olfaction. The limbic system is involved in lower order emotional processing of input from sensory systems and consists of the amygdala, mammillary bodies, stria medullaris, central gray and dorsal and ventral nuclei of Gudden. This processed information is often relayed to a collection of structures from the telencephalon, diencephalon, and mesencephalon, including the prefrontal cortex, cingulate gyrus, limbic thalamus, hippocampus including the parahippocampal gyrus and subiculum, nucleus accumbens (limbic striatum), anterior hypothalamus, ventral tegmental area, midbrain raphe nuclei, habenular commi ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |