HCRT

HCRT refers to hypocretin, also known as orexin, a pair of neuropeptides produced by neurons in the lateral hypothalamus. The HCRT gene encodes the prepro-orexin precursor, which is cleaved to yield two mature peptides, orexin-A and orexin-B. Orexins exert their effects through two G protein–coupled receptors, OX1R (HCRTR1) and OX2R (HCRTR2). Orexin-A binds both receptors with high affinity, while orexin-B has a higher relative affinity for OX2R. Orexin signaling is widely integrated into brain circuits.

In the brain, orexin-producing neurons project extensively to regions involved in arousal, energy balance, feeding, reward, and autonomic regulation. Through these pathways, the orexin system helps control wakefulness and alertness, regulates appetite and energy expenditure, modulates stress responses, and influences motivated behaviors.

Clinical relevance is most evident in narcolepsy type 1, where loss of orexin-producing neurons leads to low or undetectable cerebrospinal fluid orexin-A levels and symptoms such as excessive daytime sleepiness and cataplexy. Narcolepsy type 2 generally shows normal orexin levels. Pharmacologically, orexin receptor antagonists (such as suvorexant, lemborexant, and daridorexant) are approved for treating insomnia by dampening wake-promoting orexin signaling. Research continues into potential therapeutic applications of the orexin system for metabolic, mood, and addiction-related conditions, as well as the development of orexin-targeted therapies for other sleep disorders.