Orexin and Alzheimer’s Disease: A New Perspective

Um, Yoo Hyun; Lim, Hyun Kook

doi:10.30773/pi.2020.0136

Cited by 19 publications

(23 citation statements)

References 81 publications

(147 reference statements)

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“…Acupuncture Modulates the Orexin System. Neurons in the lateral hypothalamic region produce orexin, which has two subtypes: orexin A (OXA) and orexin B (OXB) [99]. Orexin neurons can project into the hippocampus and the medulla oblongata, and are involved in the regulation of synaptic plasticity and learning and memory.…”

Section: Acupuncture Shows Its Effects By Promoting Autophagymentioning

confidence: 99%

Acupuncture Interventions for Alzheimer’s Disease and Vascular Cognitive Disorders: A Review of Mechanisms

Yang

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Cognitive impairment (CI) related to Alzheimer’s disease (AD) and vascular cognitive disorders (VCDs) has become a key problem worldwide. Importantly, CI is a neuropsychiatric abnormality mainly characterized by learning and memory impairments. The hippocampus is an important brain region controlling learning and memory. Recent studies have highlighted the effects of acupuncture on memory deficits in AD and VCDs. By reviewing the literature published on this topic in the past five years, the present study intends to summarize the effects of acupuncture on memory impairment in AD and VCDs. Focusing on hippocampal synaptic plasticity, we reviewed the mechanisms underlying the effects of acupuncture on memory impairments through regulation of synaptic proteins, AD characteristic proteins, intestinal microbiota, neuroinflammation, microRNA expression, orexin system, energy metabolism, etc., suggesting that hippocampal synaptic plasticity may be the common as well as the core link underlying the above mechanisms. We also discussed the potential strategies to improve the effect of acupuncture. Additionally, the effects of acupuncture on synaptic plasticity through the regulation of vascular–glia–neuron unit were further discussed.

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Section: Acupuncture Shows Its Effects By Promoting Autophagymentioning

confidence: 99%

Acupuncture Interventions for Alzheimer’s Disease and Vascular Cognitive Disorders: A Review of Mechanisms

Yang

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…One emerging question in this field is whether the deficiency of orexins is protective of AD. It was found that compared with controls, narcolepsy patients showed reduced amyloid deposition and neurodegenerative marker levels [17,18].…”

Section: Oxr As a Target For Alzheimer's Disordermentioning

confidence: 99%

Orexin receptors: Targets and applications

Subramanian

Ravichandran

2021

Fundamemntal Clinical Pharma

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Over the years, elucidating targets from the neural circuits that can be used to treat disorders pertaining to the nervous system and extending their scope to other systems have always proved interesting to researchers. The role of various peptides and neurotransmitters has been elucidated and is being developed as therapeutic targets. Out of these, orexins are neuropeptides produced in the hypothalamus that stimulate a specific type of G-Protein coupled receptors (GPCR) called orexin receptors and bring about various physiological and pathological roles. Orexin receptors are of interest not only because of their wide applications such as insomnia, obesity, and inflammatory disorders but also because of their contribution to promising aspects of drug discovery such as optogenetics and their tremendous growth from the stage of being orphans to orexins. This review will discuss in detail the structure of orexin receptors, their physiological role, and various applications in disease states adding a note on agonists and antagonists and finally summarizing the recent drug approvals in the field. K E Y W O R D Sagonist, antagonist, orexin system, physiological role | INTRODUCTIONOrexins are neuropeptides involved in regulating many essential physiological functions like sleep-wake transitions, energy metabolism, cognition, and motivation.After 20 years, discovering and delineating the role of orexinergic therapeutics has stopped in research labs but this research has successfully contributed two drugs used in clinic, namely, suvorexant and lemborexant.This review will summarize the critical aspects of the orexinergic system and function and discuss the different applications of orexin receptors as drug targets. It will conclude by discussing the different agonists and antagonists at the receptor and its future prospects.

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“…20 Besides, the ApoE4 allele is likely to aggravate sleep disturbance in AD patients. 21 Some neurotransmitters, such as glutamate, 22 serotonin, 23 acetylcholine, 24 and orexin, 25 are changed or imbalanced in AD patients, and these neurotransmitters and their receptors generally are related to sleep and wakefulness. Accordingly, we discussed the evidence about sleep−wake disorders and the mechanism of AD in this review, in which we suggested some possibilities for the treatment and diagnosis of AD.…”

Section: Introductionmentioning

confidence: 99%

Sleep–Wake Disorders in Alzheimer’s Disease: A Review

Sun

Wang

Zhou

et al. 2022

ACS Chem. Neurosci.

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Alzheimer’s disease (AD) is a multifactorial disease, and it has become a serious health problem in the world. Senile plaques (SPs) and neurofibrillary tangles (NFTs) are two main pathological characters of AD. SP mainly consists of aggregated β-amyloid (Aβ), and NFT is formed by hyperphosphorylated tau protein. Sleep–wake disorders are prevalent in AD patients; however, the links and mechanisms of sleep–wake disorders on the AD pathogenesis remain to be investigated. Here, we referred to the sleep–wake disorders and reviewed some evidence to demonstrate the relationship between sleep–wake disorders and the pathogenesis of AD. On one hand, the sleep–wake disorders may lead to the increase of Aβ production and the decrease of Aβ clearance, the spreading of tau pathology, as well as oxidative stress and inflammation. On the other hand, the ApoE4 allele, a risk gene for AD, was reported to participate in sleep–wake disorders. Furthermore, some neurotransmitters, such as acetylcholine, glutamate, serotonin, melatonin, and orexins, and their receptors were suggested to be involved in AD development and sleep–wake disorders. We discussed and suggested some possible therapeutic strategies for AD treatment based on the view of sleep regulation. In general, this review explored different views to find novel targets of diagnosis and therapy for AD.

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Orexin and Alzheimer’s Disease: A New Perspective

Cited by 19 publications

References 81 publications

Acupuncture Interventions for Alzheimer’s Disease and Vascular Cognitive Disorders: A Review of Mechanisms

Acupuncture Interventions for Alzheimer’s Disease and Vascular Cognitive Disorders: A Review of Mechanisms

Orexin receptors: Targets and applications

Sleep–Wake Disorders in Alzheimer’s Disease: A Review

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