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Aging Neurosci."],"abstract":"<jats:p>Orexinergic system consisting of orexins and orexin receptors plays an essential role in regulating sleep\u2013wake states, whereas sleep disruption is a common symptom of a number of neurodegenerative diseases. Emerging evidence reveals that the orexinergic system is disturbed in various neurodegenerative diseases, including Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), Huntington\u2019s disease (HD), and multiple sclerosis (MS), whereas the dysregulation of orexins and\/or orexin receptors contributes to the pathogenesis of these diseases. In this review, we summarized advanced knowledge of the orexinergic system and its role in sleep, and reviewed the dysregulation of the orexinergic system and its role in the pathogenesis of AD, PD, HD, and MS. 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