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

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

  • Liblau RS Centre de Physiopathologie Toulouse Purpan, INSERM UMR1043, CNRS UMR5282, Université de Toulouse III, Toulouse, France.
  • Vassalli A Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
  • Seifinejad A Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
  • Tafti M Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland; Center for Investigation and Research in Sleep, Vaud University Hospital, Lausanne, Switzerland. Electronic address: mehdi.tafti@unil.ch.
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  • 2015-03-03
Published in:
  • The Lancet. Neurology. - 2015
Animals
Brain
Cataplexy
Humans
Intracellular Signaling Peptides and Proteins
Narcolepsy
Nerve Net
Neuropeptides
Orexins
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.rero.ch/global/documents/248423
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