0055 An Orexin 2 Receptor-selective Agonist, TAK-925, Ameliorates Narcolepsy-like Symptoms and Obesity in Orexin/ataxin-3 Transgenic Mice
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چکیده
منابع مشابه
Nonpeptide orexin type-2 receptor agonist ameliorates narcolepsy-cataplexy symptoms in mouse models.
Narcolepsy-cataplexy is a debilitating disorder of sleep/wakefulness caused by a loss of orexin-producing neurons in the lateroposterior hypothalamus. Genetic or pharmacologic orexin replacement ameliorates symptoms in mouse models of narcolepsy-cataplexy. We have recently discovered a potent, nonpeptide OX2R-selective agonist, YNT-185. This study validates the pharmacological activity of this ...
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Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy, direct onsets of rapid eye movement (REM) sleep from wakefulness (DREMs) and deficiency of orexins, neuropeptides that promote wakefulness largely via activation of histamine (HA) pathways. The hypothesis that the orexin defect can be circumvented by enhancing HA release was explored in narcoleptic mice and patients u...
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Orexins (hypocretins) are a pair of neuropeptides implicated in energy homeostasis and arousal. Recent reports suggest that loss of orexin-containing neurons occurs in human patients with narcolepsy. We generated transgenic mice in which orexin-containing neurons are ablated by orexinergic-specific expression of a truncated Machado-Joseph disease gene product (ataxin-3) with an expanded polyglu...
متن کاملOrexin deficiency and narcolepsy.
Orexin deficiency results in the sleep disorder narcolepsy in many mammalian species, including mice, dogs, and humans, suggesting that the orexin system is particularly important for normal regulation of sleep/wakefulness states, and especially for maintenance of wakefulness. This review discusses animal models of narcolepsy; the contribution of each orexin receptor subtype to the narcoleptic ...
متن کاملNarcolepsy: selective hypocretin (orexin) neuronal loss and multiple signaling deficiencies.
Narcolepsy is a usually sporadic disorder with a prevalence of 1:2,000—its importance is not just medical, for it has a major psychosocial impact. Narcolepsy, as described by Gélineau in 1880, presents with excessive daytime sleepiness (EDS) and cataplexy.1 These features and typical findings on multiple sleep latency tests (mean sleep latency 5 to 8 minutes or 2 sleep onset REM periods in 70 t...
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ژورنال
عنوان ژورنال: Sleep
سال: 2019
ISSN: 0161-8105,1550-9109
DOI: 10.1093/sleep/zsz067.054