Hypocretin (orexin) biology and the pathophysiology of narcolepsy with cataplexy.

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State: Public
Version: Final published version
Serval ID
serval:BIB_CE92DA077804
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Hypocretin (orexin) biology and the pathophysiology of narcolepsy with cataplexy.
Journal
Lancet. Neurology
Author(s)
Liblau R.S., Vassalli A., Seifinejad A., Tafti M.
ISSN
1474-4465 (Electronic)
ISSN-L
1474-4422
Publication state
Published
Issued date
2015
Volume
14
Number
3
Pages
318-328
Language
english
Abstract
The discovery of hypocretins (orexins) and their causal implication in narcolepsy is the most important advance in sleep research and sleep medicine since the discovery of rapid eye movement sleep. Narcolepsy with cataplexy is caused by hypocretin deficiency owing to destruction of most of the hypocretin-producing neurons in the hypothalamus. Ablation of hypocretin or hypocretin receptors also leads to narcolepsy phenotypes in animal models. Although the exact mechanism of hypocretin deficiency is unknown, evidence from the past 20 years strongly favours an immune-mediated or autoimmune attack, targeting specifically hypocretin neurons in genetically predisposed individuals. These neurons form an extensive network of projections throughout the brain and show activity linked to motivational behaviours. The hypothesis that a targeted immune-mediated or autoimmune attack causes the specific degeneration of hypocretin neurons arose mainly through the discovery of genetic associations, first with the HLA-DQB1*06:02 allele and then with the T-cell receptor α locus. Guided by these genetic findings and now awaiting experimental testing are models of the possible immune mechanisms by which a specific and localised brain cell population could become targeted by T-cell subsets. Great hopes for the identification of new targets for therapeutic intervention in narcolepsy also reside in the development of patient-derived induced pluripotent stem cell systems.
Pubmed
Web of science
Create date
20/03/2015 8:56
Last modification date
20/08/2019 16:49
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