Man with narcolepsy type 1 sitting in a chair and talking in a support group

IT TAKES UNDERSTANDING
MORE ABOUT OREXIN

to know there's a reason for their
NT1 symptoms

OREXIN IS A KEY REGULATOR OF THE SLEEP-WAKE CYCLE

Adapted from Toor B, et al. Front Neurol Neurosci. 2021,1 De Luca R, et al. Nat Commun. 2022,2 Sakurai T. Nat Rev Neurosci. 2007,3 and Mahoney CE, et al. Nat Rev Neurosci. 2019.4  Depiction is for illustrative purposes.

Orexin signaling is impaired in people with NT15

Orexin (hypocretin) is a key neurotransmitter released by orexinergic neurons located in the lateral hypothalamus. Loss of orexin is thought to cause a disruption in orexin signaling, the underlying cause of narcolepsy type 1 (NT1), which destabilizes the sleep-wake cycle. It is also thought to play a role in cognitive and mood dysfunction, muscle atonia, and energy imbalance.1,2,4

Diminished orexin signaling is believed to have a downstream effect on other neurotransmitters, including histamine. This is thought to result in a range of symptoms that may vary in scope and severity from person to person with NT1 and include1,6:

  • Excessive daytime sleepiness (EDS)
  • Cataplexy
  • Sleep paralysis
  • Hypnagogic and hypnopompic hallucinations
  • Disrupted nighttime sleep

Cumulatively, these symptoms can have far-reaching effects, such as difficulty with sustained attention, depression, and limited ability to engage in work, school, social activities, and relationships.1,4,7

Woman with narcolepsy type 1 jumping and one-hand shooting a basketball into a hoop
Woman with narcolepsy type 1 studying at her desk

Areas affected by impaired orexin signaling

Wakefulness

due to a disruption in downstream signaling1,2

An alarm clock icon

Cognition

as well as working memory and the ability to sustain attention1

A brain inside a person's head icon

Mood

and the regulation of emotion4

A tired person feeling moody icon

Sleep quality

due to the destabilization of the boundary between sleep (NREM, REM) and wakefulness, leading to disrupted nighttime sleep, sleep paralysis, and hallucinations2

A person laying in bed and a clock on the wall icon

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NREM, non-rapid eye movement; REM, rapid eye movement.

References

1. Toor B, Ray LB, Pozzobon A, Fogel SM. Sleep, orexin and cognition. Front Neurol Neurosci. 2021;45:38-51. doi:10.1159/000514960 2. De Luca R, Nardone S, Grace KP, et al. Orexin neurons inhibit sleep to promote arousal. Nat Commun. 2022;13(1):4163. doi:10.1038/s41467-022-31591-y 3. Sakurai T. The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci. 2007;8(3):171-181. doi:10.1038/nrn2092 4. Mahoney CE, Cogswell A, Koralnik IJ, Scammell TE. The neurobiological basis of narcolepsy. Nat Rev Neurosci. 2019;20(2):83-93. doi:10.1038/s41583-018-0097-x 5. Scammell TE. Narcolepsy. N Engl J Med. 2015;373(27):2654-2662. doi:10.1056/NEJMra1500587 6. Morse AM, Kim SY, Harris S, Gow M. Narcolepsy: beyond the classic pentad. CNS Drugs. 2025;39(suppl 1):S9-S22. doi:10.1007/s40263-024-01141-9 7. Davidson RD, Biddle K, Nassan M, Scammell TE, Zhou ES. The impact of narcolepsy on social relationships in young adults. J Clin Sleep Med. 2022;18(2):2751-2761. doi:10.5664/jcsm.10212