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The neurobiological basis of narcolepsy
Open accessAbstract
Narcolepsy is the most common neurological cause of chronic sleepiness. The discovery about 20 years ago that narcolepsy is caused by selective loss of the neurons producing orexins (also known as hypocretins) sparked great advances in the field. Here, we review the current understanding of how orexin neurons regulate sleep-wake behaviour and the consequences of the loss of orexin neurons. We also summarize the developing evidence that narcolepsy is an autoimmune disorder that may be caused by a T cell-mediated attack on the orexin neurons and explain how these new perspectives can inform better therapeutic approaches.
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“Orexin neurons are both necessary and sufficient for wakefulness.”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [36]
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“Without orexin or with altered orexin receptors, humans and animals experience narcolepsy,34–39”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [36]
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Metadata
- Authors
- Mahoney, C. E., Cogswell, A., Koralnik, I. J., & Scammell, T. E.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Rush University Medical Center (US)
- Corresponding author
- Scammell, Thomas E.
- Venue
- Nature Reviews Neuroscience
- Published
- 2018-12-13
- Volume
- 20
- Issue
- 2
- Pages
- 83-93
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- PMC
- PMC6492289
- OpenAlex
- W2904386018
- Cited by
- 289
- References
- 209
- Citations by year
- 2026: 30 · 2025: 58 · 2024: 45 · 2023: 43 · 2022: 43 · 2021: 30 · 2020: 20 · 2019: 19
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL095491)
- National Institute of Neurological Disorders and Stroke (R21NS099787, R01NS106032)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- narcolepsy, orexin neurons, orexin, sleep-wake regulation, autoimmune disease, neurodegeneration, treatment options
- MeSH terms
- Orexins, Animals, Autoimmune Diseases, Humans, Narcolepsy, Nervous System, Neurobiology
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