The role of orexin in Alzheimer disease: From sleep-wake disturbance to therapeutic target

Neurosci Lett. 2021 Nov 20:765:136247. doi: 10.1016/j.neulet.2021.136247. Epub 2021 Sep 14.

Abstract

Accumulating evidence has shown that sleep disturbance is a common symptom in Alzheimer's disease (AD), which is regarded as a modifiable risk factor for AD. Orexin is a key modulator of the sleep-wake cycle and has been found to be dysregulated in AD patients. The increased orexin in cerebrospinal fluid (CSF) is associated with decreased sleep efficiency and REM sleep, as well as cognitive impairment in AD patients. The orexin system has profuse projections to brain regions that are implicated in arousal and cognition and has been found to participate in the progression of AD pathology. Conversely the orexin receptor antagonists are able to consolidate sleep and reduce AD pathology. Therefore, improved understanding of the mechanisms linking orexin system, sleep disturbance and AD could make orexin receptor antagonists a promising target for the prevention or treatment of AD.

Keywords: Alzheimer's disease; Cognition; Orexin; Sleep-wake disturbance; Therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Cognition / drug effects
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / etiology
  • Disease Models, Animal
  • Humans
  • Orexin Receptor Antagonists / pharmacology
  • Orexin Receptor Antagonists / therapeutic use*
  • Orexins / antagonists & inhibitors
  • Orexins / metabolism*
  • Sleep Wake Disorders / drug therapy
  • Sleep Wake Disorders / etiology*
  • Sleep Wake Disorders / pathology
  • Sleep, REM / drug effects

Substances

  • Amyloid beta-Peptides
  • HCRT protein, human
  • Orexin Receptor Antagonists
  • Orexins