ArticleScientific reports2016
Orexin signaling regulates both the hippocampal clock and the circadian oscillation of Alzheimer's disease-risk genes.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 87 citations in OpenAlex.
- In Silico to In Cerebro-Development of the Orexin Receptor Antagonist "Photorexant" for Photomodulation In Vitro and in Mouse Brains.Angewandte Chemie (International ed. in English) · 2026Article
- Circadian clock genes and insomnia: molecular mechanisms and therapeutic implications.Annals of medicine · 2025Review
- Circadian rhythm of amyloid-β in the olfactory bulb and cerebellum of wild-type and APPxPS1 knock-in mice indicates a loss of rhythmicity in regions more vulnerable to amyloid pathology.Biogerontology · 2025Article
- Sleep as the Foundation of Brain Health.Seminars in neurology · 2025Review
- Modelling orexinergic system in ageing in the African turquoise killifish.Biogerontology · 2025Review
- The interaction between orexin, sleep deprivation and Alzheimer's disease: Unveiling an Emerging Connection.The journal of physiological sciences : JPS · 2025Review
- Epigenetic Mechanisms in the Transcriptional Regulation of Circadian Rhythm in Mammals.Biology · 2025Review
- Neuropathology-based approach reveals novel Alzheimer's Disease genes and highlights female-specific pathways and causal links to disrupted lipid metabolism: insights into a vicious cycle.Acta neuropathologica communications · 2025Article
- Dual orexin receptor antagonists as promising therapeutics for Alzheimer's disease.Npj biological timing and sleep · 2025Review
- Circadian system and aging: where both times interact.Frontiers in aging · 2025Review
- From genes to drugs: targeting Alzheimer's with circadian insights.Frontiers in aging neuroscience · 2025Article
- The Aggravating Role of Failing Neuropeptide Networks in the Development of Sporadic Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Review
- Article
- Cannabinoid and Orexigenic Systems Interplay as a New Focus of Research in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Circadian Regulation of Apolipoproteins in the Brain: Implications in Lipid Metabolism and Disease.International journal of molecular sciences · 2023Review
- Diurnal Characteristics of the Orexin System Genes and Its Effects on Pathology at Early Stage in 3xTg-AD Mice.Neuromolecular medicine · 2023Article
- Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer's disease.Cell metabolism · 2023Article
- Disturbed circadian rhythm and retinal degeneration in a mouse model of Alzheimer's disease.Acta neuropathologica communications · 2023Article
- Circadian dysfunction and Alzheimer's disease - An updated review.Aging medicine (Milton (N.S.W)) · 2023Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is a circadian clock-related disease. However, it is not very clear whether pre-symptomatic AD leads to circadian disruption or whether malfunction of circadian rhythms exerts influence on development of AD. Here, we report a functional clock that exists in the hippocampus. This oscillator both receives input signals and maintains the cycling of the hippocampal Per2 gene. One of the potential inputs to the oscillator is orexin signaling, which can shorten the hippocampal clock period and thereby regulate the expression of clock-controlled-genes (CCGs). A 24-h time course qPCR analysis followed by a JTK_CYCLE algorithm analysis indicated that a number of AD-risk genes are potential CCGs in the hippocampus. Specifically, we found that Bace1 and Bace2, which are related to the production of the amyloid-beta peptide, are CCGs. BACE1 is inhibited by E4BP4, a repressor of D-box genes, while BACE2 is activated by CLOCK:BMAL1. Finally, we observed alterations in the rhythmic expression patterns of Bace2 and ApoE in the hippocampus of aged APP/PS1dE9 mice. Our results therefore indicate that there is a circadian oscillator in the hippocampus whose oscillation could be regulated by orexins. Hence, orexin signaling regulates both the hippocampal clock and the circadian oscillation of AD-risk genes.
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