Orexin deficiency and narcolepsy

•Loss of orexin neurons causes narcolepsy in humans and other mammalian species.•Orexin deficient mice show phenotypes that have parallels to the human narcolepsy.•90% of narcolepsy patients have decreased orexin A levels in cerebrospinal fluid.•Orexin receptors would provide promising targets for new drugs for sleep disorders.

Orexin deficiency results in the sleep disorder narcolepsy in many mammalian species, including mice, dogs, and humans, suggesting that the orexin system is particularly important for normal regulation of sleep/wakefulness states, and especially for maintenance of wakefulness. This review discusses animal models of narcolepsy; the contribution of each orexin receptor subtype to the narcoleptic phenotypes; and the etiology of orexin neuronal death. It also raises the possibility of novel therapies targeting the orexin system for sleep disorders including insomia and narcolepsy-cataplexy.