睡眠机制知识库

睡眠与做梦:解开发作性睡病之谜

To sleep and dream: Unraveling narcolepsy.

原始研究开放获取
作者
Friedman JM
期刊
Proceedings of the National Academy of Sciences of the United States of America
出处
2026; 123(37); e2622458123
DOI
10.1073/pnas.2622458123
PMID
42713970

一句话摘要

记述 Mignot 与柳泽正史以两条完全不同的路径确立发作性睡病发病机制:前者用正向遗传学在犬遗传性发作性睡病中定位食欲素受体 2 缺陷,后者纯化孤儿受体的脑内配体并用反向遗传学证明其敲除导致小鼠发作性睡病。

为什么重要

记录了两条独立技术路线殊途同归地证明「食欲素信号维持觉醒、其缺失导致发作性睡病」这一经典发现史,是理解该领域证据如何被确立的第一手叙述。

英文摘要原文

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.

所属章节

睡眠障碍病理生理 神经递质调控(食欲素、褪黑素、GABA)

发作性睡病 食欲素 历史 配体发现

条目编号 P093 · 元数据经 Crossref / Europe PMC 回查