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Chapter 24 - Orexin (hypocretin)and narcolepsy

from Section 5 - Narcolepsyand hypersomnias

Published online by Cambridge University Press:  05 November 2013

By
Takeshi Sakurai  and
Seiji Nishino
Edited by
Paul Shaw ,
Mehdi Tafti  and
Michael J. Thorpy
Paul Shaw
Affiliation:
University of Washington, St Louis
Mehdi Tafti
Affiliation:
University of Lausanne
Michael J. Thorpy
Affiliation:
Sleep-Wake Disorders Center, Albert Einstein College of Medicine, New York
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Summary

This chapter discusses the relationship between orexin and narcolepsy as a condition with orexin deficiency, as well as the physiological roles of these peptides in regulation of sleep/wakefulness states, and the therapeutic potential of drugs that target orexin receptors. The actions of orexins are mediated via two G-protein coupled receptors (GPCRs), orexin 1 (OXR-1) and orexin 2 (OXR-2) receptors. The link between orexin dysfunction and narcolepsy has been subsequently supported by studies in human narcolepsy patients. Due to its strong association with certain human leukocyte antigen (HLA) alleles, it has been speculated that narcolepsy results from selective immune-mediated degeneration of orexin neurons. Narcolepsy has been established as a condition resulting from orexin deficiency. This means that the orexin system is a critical component for maintenance of wakefulness, and the orexin system has important diagnostic and therapeutic value.

Keywords

monozygotic studyquantitative trait locus analysisgene expressiongeneticsmicesleepcandidate gene approachdizygotic studyelectroencephalogram
Type
Chapter
Information
The Genetic Basis of Sleep and Sleep Disorders , pp. 242 - 253
Publisher: Cambridge University Press
Print publication year: 2013

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