To sleep and dream: Unraveling narcolepsy

• 成果类型: Article
• 署名作者: Friedman, Jeffrey M.
• 署名单位: Rockefeller University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2622458123
• 发表日期: 2026-09-15
• 页码: e2622458123
• 关键词: PEPTIDES; HYPOCRETINS; Mutation; genetics; OREXINS

摘要

In an extraordinary convergence, Emmanuel Mignot and Masashi Yanagisawa employed two entirely different approaches to establish the pathogenesis of narcolepsy, a devastating sleep disorder associated with overwhelming sleep attacks, cataplexy, episodes with sudden loss of muscle tone, and hallucinations resulting from dreaming while awake. Yanagisawa purified brain ligands for orphan G protein-coupled receptors identifying a peptide, orexin, and then used reverse genetics to show that a knockout of the neuropeptide caused narcolepsy in mice. Mignot used forward genetics to identify genetic defects in the orexin receptor 2 in a hereditable form of canine narcolepsy. Together, they showed that orexin signaling in the brain maintains wakefulness and that orexin deficiency causes narcolepsy. This has led to new, effective treatments to induce sleep or maintain wakefulness. Their discoveries have elucidated a novel neural and molecular mechanism that maintains arousal, suppresses sleep, and controls the onset of our dreams.