Recent Insights on the Role of Nuclear Receptors in Alzheimer’s Disease: Mechanisms and Therapeutic Application

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1207 - 1207

Published: Jan. 30, 2025

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate a broad array of biological processes, including inflammation, lipid metabolism, cell proliferation, and apoptosis. Among the diverse family NRs, peroxisome proliferator-activated (PPARs), estrogen receptor (ER), liver X (LXR), farnesoid (FXR), retinoid (RXR), aryl hydrocarbon (AhR) have garnered significant attention for their roles in neurodegenerative diseases, particularly Alzheimer’s disease (AD). NRs influence pathophysiology AD through mechanisms such as modulation amyloid-beta (Aβ) deposition, regulation inflammatory pathways, improvement neuronal function. However, dual role progression, where some may exacerbate while others offer therapeutic potential, presents critical challenge application treatment. This review explores functional diversity highlighting involvement AD-related processes discussing prospects NR-targeting strategies. Furthermore, key challenges, necessity precise identification beneficial detailed structural analysis molecular dynamics simulations, further investigation NR AD, tau pathology autophagy, also discussed. Collectively, continued research is essential to clarify ultimately facilitating potential use diagnosis, prevention, treatment AD.

Language: Английский

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Melatonin Regulates Glymphatic Function to Affect Cognitive Deficits, Behavioral Issues, and Blood–Brain Barrier Damage in Mice After Intracerebral Hemorrhage: Potential Links to Circadian Rhythms

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(2)

Published: Feb. 1, 2025

ABSTRACT Background Intracerebral hemorrhage (ICH) is a life‐threatening cerebrovascular disorder with no specific pharmacological treatment. ICH causes significant behavioral deficits and cognitive impairments. Recent research suggests that circadian rhythm regulation could be promising therapeutic strategy for ICH. Melatonin has been shown to alleviate glymphatic system (GS) dysfunction by regulating rhythms, thereby improving depressive‐like behaviors postoperative sleep disorders in mice. However, its application treatment mechanisms are not well understood. Methods models were created 8‐to‐10‐week‐old mice using collagenase injection. Circadian modulation was tested melatonin luzindole. Behavioral impairments assessed the modified neurological severity score, corner test, novel object recognition test. Brain water content measured dry/wet weight method, cerebral perfusion blood flow measurements. GS function evaluated RITC‐dextran Evans blue assays. Immunofluorescence western blotting used analyze BBB permeability. Results restored transport after ICH, promoting hematoma edema absorption, reducing damage, outcomes. luzindole partially blocked these benefits reversed neuroprotective effects. Conclusion affect function, permeability, cognitive‐behavioral outcomes The underlying mechanism may involve of rhythms.

Language: Английский

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Exploring the nexus: Sleep disorders, circadian dysregulation, and Alzheimer’s disease

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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