The neurobiological basis of narcolepsy

• Published in: Nature reviews. Neuroscience Vol. 20; no. 2; pp. 83 - 93
• Main Authors: Mahoney, Carrie E., Cogswell, Andrew, Koralnik, Igor J., Scammell, Thomas E.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2019; Nature Publishing Group
• Subjects: 631/378/1385/2642; 631/378/1385/2643; 631/378/1385/519; 692/699/375/1816; Animal Genetics and Genomics; Animals; Autoimmune Diseases; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Humans; Immune system; Lymphocytes T; Narcolepsy; Narcolepsy - metabolism; Narcolepsy - pathology; Narcolepsy - physiopathology; Nervous System - metabolism; Nervous System - pathology; Nervous System - physiopathology; Neurobiology; Neurons; Neurosciences; Orexins; Orexins - metabolism; Review Article; Sleep; Sleep and wakefulness; Sleep disorders; T cells
• ISSN: 1471-003X; 1471-0048; 1469-3178
• DOI: 10.1038/s41583-018-0097-x

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. Narcolepsy is a sleep disorder caused by selective loss of orexin-producing neurons. Scammell and colleagues describe the functions of orexin neurons and the effects of their loss and review evidence implicating the immune system in the pathogenesis of the disorder.