Orexin Peptides: Wakefulness, Appetite and Narcolepsy Research

Orexin Peptides: Wakefulness, Appetite and Narcolepsy Research

The orexin system — comprising Orexin A (hypocretin-1) and Orexin B (hypocretin-2) and their receptors OX1R and OX2R — is one of the most significant discoveries in neuroscience of the past 30 years.

Discovery

Orexins were simultaneously discovered in 1998 by two independent research groups: Luis de Lecea's group (who named them hypocretins) and Masashi Yanagisawa's group (who named them orexins). The peptides are produced exclusively by neurons in the lateral hypothalamus.

Narcolepsy Connection

The critical role of orexin signalling in maintaining wakefulness was established when researchers discovered that narcoleptic dogs carry mutations in OX2R, and that orexin knockout mice display a narcolepsy-like syndrome.

Research Significance

The orexin system is now a validated therapeutic target, with orexin receptor antagonists approved for insomnia treatment. Research with Orexin A and B peptides continues to explore their roles in sleep architecture, energy metabolism, and reward signalling.