Neuropeptides that play a significant role in the regulation of food intake and sleep-wakefulness, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions. A broader role in the homeostatic regulation of energy metabolism, autonomic function, hormonal balance and the regulation of body fluids, is also suggested. Orexin-A binds to both OX1R and OX2R with a high affinity, whereas orexin-B binds only to OX2R with a similar high affinity.

1. Like OX1R, OX2R has an N-terminal helix important for binding the orexin peptide. PMID: 29225076
2. this study, both Perry syndrome and MSA had significantly reduced orexin immunoreactivity in the nucleus basalis of Meynert. PMID: 28651750
3. Orexin A levels correlated with age in females and were significantly elevated in PWS even after these effects were controlled. These findings support the hypothesis that dysregulation of orexin signaling may contribute to behavioral problems and hyperphagia in PWS. PMID: 27214028
4. Orexin levels do not play a role in the control of nocturnal blood pressure dipping in patients with narcolepsy type 1. PMID: 29023559
5. No association was observed between rs9902709 in HCRT and OSAHS (obstructive sleep apnea) risk in Chinese Han population. PMID: 27509181
6. findings show that in few patients with narcolepsy with cataplexy, symptoms and CSF hypocretin-1 and histamine levels can change over time PMID: 28364477
7. The plasma orexin-A level was associated with physical activity in obese and overweight people, including many aspects of daily life, such as working, domestic work, and walking especially. PMID: 27038345
8. Orexin-A is associated with increased phosphorylated P-Tau in normal elderly individuals. Increases in orexin-A and P-Tau might be a consequence of the reduction in the proportion of the deeper, more restorative slow wave sleep and rapid eye movement sleep reported with aging. PMID: 26951396
9. actigraphy gives additional information about the stabilization of sleep in patients with narcolepsy type 1; very low hypocretin levels associate with more wake intruding into sleep PMID: 26856902
10. Exercise induced a significant increase in plasmatic orexin A with a peak at 3o minutes. PMID: 27665420
11. There was also a negative correlation between Epworth sleepiness scale scores and orexin levels in Prader-Willi syndrome patients. Decreased cerebrospinal fluid orexin levels in Prader-Willi syndrome may play an important role in severity of obesity and excessive daytime sleepiness. PMID: 26738920
12. orexin system may be involved even in the earliest stages of AD, resulting in prolonged sleep latency, reduced sleep efficiency, and REM sleep impairment. PMID: 26973111
13. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation is highly unlikely to be caused by mutations in the exons of the gene for hypocretin. PMID: 26555080
14. Data indicate a positive correlation of nesfatin-1 and a negative correlation of orexin-A with body mass index. PMID: 26831553
15. This study showed that orexin A induced autophagy through the ERK pathway in HCT116 human colon cancer cells. PMID: 26572581
16. Low circulating Orexin A was found to be significantly associated with hyperlipidemia, obesity and obesity-related disorders in North Indian premenopausal women. PMID: 27530010
17. This is the first time a seasonal variation of hcrt-1 levels has been shown, demonstrating that the hcrt system is, like other neurotransmitter systems, subjected to long term modulation PMID: 27008404
18. Significantly reduced csf levels of hypocretin-1 were found in cluster headache patients compared with controls. PMID: 25492975
19. Study shows Ox immunoreactivity is decreased in the hypothalamus and pontine nuclei of infants who died from sudden infant death syndrome PMID: 25953524
20. Results from homology and docking modeling show two alternative binding modes for orexin-A into orexin 1 receptor in concordance with what is known of G protein coupled receptors activation in general and the mutational data. PMID: 25957175
21. Patients with schizophrenia had a significantly higher plasma HCRT level than healthy controls. Patients in the high-orexin subgroup had significantly fewer negative and disorganized symptoms, and tended to have fewer perseverative errors. PMID: 25560205
22. Data suggest that interaction between the nociceptin/nociceptin receptor system and the orexin/orexin receptor system in neurons of the hypothalamus positively and negatively modulate complex and integrated responses to stress. [REVIEW] PMID: 25677777
23. Decrease in Ox expression with normal human maturation and aging. This may contribute to changes in sleep regulation during development and with aging. PMID: 25212464
24. Orexin A upregulates the protein expression of OX1R and enhances the proliferation of SGC-7901 gastric cancer cells through the ERK signaling pathway. PMID: 25515760
25. Orexin receptor binding was strongly dependent on the extracellular Ca(2+) concentration. PMID: 25132134
26. autoimmune encephalitis and neuromyelitis optica patients had significantly lower serum orexin-A levels than both healthy controls and narcolepsy patients PMID: 25218417
27. No significant differences were found in the distribution of either genotypic or allelic frequencies between Alzheimer's disease cases and controls in the HCRT polymorphisms. PMID: 24969517
28. Hypocretin, MOG, or DNMT1 mutations are exceptional findings in DQB1*06:02 negative narcolepsy cases with hypocretin deficiency PMID: 25197808
29. In patients with narcolepsy with cataplexy, deficient CSF HCRT levels were correlated with lower muscle sympathetic nerve activity and heart rate. PMID: 25098533
30. the first report clarifying the substantial loss of Hcrt neurons in the LHT and of Hcrt axonal terminals in the LC in DLB and the correlation between the severity of Hcrt neuronal loss and progression of neurofibrillary pathology. PMID: 24704327
31. Rapid postoperative increases in plasma Orexin are associated with better improvement of glucose and lipid profiles following bariatric surgery. PMID: 24400115
32. lumbar ORX-A levels are significantly higher than ventricular levels in idiopathic normal pressure hydrocephalus patients. PMID: 24172541
33. OX1 is upregulated in the transgenic mouse suprachiasmatic nucleus at dusk. PMID: 24599460
34. The orexin-A levels were significantly lower in patients with frontotemporal dementia compared to controls. PMID: 23813609
35. Sequencing of a large number of early-onset narcolepsy subjects revealed three novel nonsynonymous substitutions within the preprohypocretin protein, two of which were only found in patients with early-onset narcolepsy. PMID: 23643651
36. It regulates energy and glucose metabolism.(review) PMID: 24334931
37. serum and cerebrospinal fluid orexin-A concentrations decrease after cerebral ischaemia and may play a role in the development of brain injury. PMID: 23569032
38. Cerebrospinal fluid (CSF) levels were measured in 33 patients with Alzheimer's disease (AD) and 33 healthy subjects, to investigate the role of MCH and HCRT-1 in AD. PMID: 23667582
39. Maternal serum OXA levels decrease, and fetal serum OXA levels increase in women with gestational diabetes. PMID: 22889404
40. A sensor platform capable of rapid biomarker detection specific for detecting neuropeptide orexin A, is found in blood and saliva as an indicator of fatigue and cognitive performance, and can be easily expanded. PMID: 23509980
41. Our results indicate that serum OXA levels decrease in the serum of women with PCOS. PMID: 23350701
42. Serum S100B and orexin A levels may be helpful in differentiating parasomnic pediatric patients with and without epilepsy. PMID: 23406753
43. melatonin and hypocretin, may affect Alzheimer's disease pathophysiology, as this may provide a role for lack of sleep and circadian rhythm deterioratio--REVIEW PMID: 22575905
44. the changes in the levels of two hypothalamic neuropeptides, hypocretin-1 and melanin-concentrating hormone, measured in the human amygdala, are reported. PMID: 23462990
45. Substitution of the deficient neuropeptides by hypocretin agonists may become the causal treatment strategy for narcolepsy--{REVIEW} PMID: 22696207
46. [review] The role of neuropeptide orexins has been investigated in many functions mediated by the central nervous system, including sleep and wakefulness, appetite/metabolism, stress response, reward/addiction, and analgesia. PMID: 23034387
47. There was a statistically significant difference in orexin expression between nicotine dependent smokers, non-smokers, and cannabis dependent subjects. Promoter methylation did not differ between groups. PMID: 22846875
48. We conclude that the hypocretin system is affected in advanced AD PMID: 21546124
49. Lower levels of CSF orexin are specific to dementia with Lewy body (DLB) versus Alzheimer's disease (AD) and appear unrelated to Abeta1-42 and alpha-synuclein levels in AD and DLB. PMID: 22207004
50. a functional locus within the HCRT gene, which may act to increase HCRT expression and lead to a protective effect against the development of OSAS. PMID: 22302634

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Rough endoplasmic reticulum. Cytoplasmic vesicle. Cell junction, synapse.

Orexin family

Abundantly expressed in subthalamic nucleus but undetectable in other brain regions tested (hypothalamus was not tested) and in heart, placenta, lung, liver, skeletal muscle, kidney and pancreas.

HGNC: 4847

OMIM: 161400

KEGG: hsa:3060

STRING: 9606.ENSP00000293330

UniGene: Hs.158348