hypocretin; orexin (HCRT, OX, PPORX, PPOX)
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Function
- precursor to peptide neurotransmitters
- may play a role in sleep
- may play role in appetite
- may have broader role in homeostatic regulation of
- energy metabolism
- autonomic function,
- hormonal balance
- regulation of body fluids
- preprohypocretin gives rise to orexin-A (Hcrt1) & orexin-B (Hcrt2)
- orexin-A binds to both OX1R & OX2R with a high affinity
- orexin-B binds only to OX2R with a similar high affinity
- specific enzymatic cleavages at paired basic residues yield the different active peptides
Structure
- structurally similar to secretin
- belongs to the orexin family
Compartment
- rough endoplasmic reticulum (putative)
- cytoplasmic vesicle (putative)
- cell junction, synapse
- associated with perikaryal rough endoplasmic reticulum as well as cytoplasmic large granular vesicles at synapses (putative)
Expression
- abundantly expressed in subthalamic nucleus[4]
- no expression in other brain regions tested[4] (hypothalamus was not tested)[4]
- not expressed in heart, placenta, lung, liver, skeletal muscle, kidney or pancreas
- expressed in hypothalamus
- concentrated in perifornical nucleus & dorsal, lateral & posterior hypothalamus
- dense localization in monoaminergic neurons
- expressed in pons[1]
Pathology
- deficiency of hypocretins (low CSF levels) or defect in hypocretins may result in narcolepsy
- hypocretins/ orexins are absent &/or greatly diminished in the brain & CSF of most patients with narcolepsy
- higher CSF orexin levels possible linked to sleep disorder in patients with Alzheimer's disease
Pharmacology
- orexin receptor antagonist suvorexant FDA-approved to treat insomnia[6]
Notes
- Orexin from the Greek orexis meaning appetite. orexin-A = hypocretin-1; orexin-B = hypocretin-2
More general terms
Additional terms
References
- ↑ 1.0 1.1 Journal Watch 20(21):170, 2000
- ↑ Peyron C et al A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nature Med 6:991,2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10973318
- ↑ Sakurai T et al Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92:573, 1998 PMID: https://www.ncbi.nlm.nih.gov/pubmed/9491897
- ↑ 4.0 4.1 4.2 4.3 UniProt http://www.uniprot.org/uniprot/O43612.html
- ↑ Protein Spotlight; qui dort dine - Issue 15 of October 2001 http://web.expasy.org/spotlight/back_issues/sptlt015.shtml
- ↑ 6.0 6.1 FDA News Release. August 13, 2014 FDA approves new type of sleep drug, Belsomra http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm409950.htm
- ↑ Liguori C et al. Orexinergic system dysregulation, sleep impairment, and cognitive decline in Alzheimer disease. JAMA Neurol 2014 Oct 13; PMID: https://www.ncbi.nlm.nih.gov/pubmed/25322206
Ferini-Strambi L. Possible role of orexin in the pathogenesis of Alzheimer disease. JAMA Neurol 2014 Oct 13 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25317720