Editors' ChoiceNeuroimmunology

Autoimmunity in narcolepsy

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Science  07 Oct 2016:
Vol. 354, Issue 6308, pp. 78
DOI: 10.1126/science.354.6308.78-c

Narcolepsy is a neurological disorder characterized by sleep that can strike at any time, lasting from seconds to minutes. Most narcoleptics experience loss of muscle tone (cataplexy) and have low levels of orexin (hypocretin), a neurotransmitter that promotes wakefulness. Destruction of orexin-producing neurons in the brain is thought to cause narcolepsy. Bernard-Valnet et al. report that cytotoxic T cells infiltrate the brain, interact with orexin-producing neurons, and destroy them. The authors engineered a mouse model to express a specific self-antigen in hypothalamic neurons that produce orexin. Cytotoxic T cells that recognize this antigen infiltrated the brain and destroyed these neurons. Consequently, the animals had sleep attacks and cataplectic episodes. This potential autoimmune mechanism may provide targets for narcolepsy therapies.

Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1603325113 (2016).

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