Involvement of hypocretins/orexins in sleep disorders and narcolepsy.

The orexins/hypocretins are novel peptide neurotransmitters first characterized in 1998. The cell bodies of the neurons releasing them are localized exclusively in the posterior and lateral hypothalamus although they send out projections which innervate the whole central nervous system. They have recently attracted a great deal of interest in the neuroscience and medical community due to the finding that a reduction of orexin/hypocretins levels occurs in most human cases of the sleep disorder narcolepsy. A flurry of recent experimental data has begun to shed light on the normal physiological functioning of this system and how its loss leads to narcolepsy. Preliminary findings also indicate that it may malfunction in a variety of other conditions where the normal sleep-wake cycle is compromised.