TMF Attenuates Cognitive Impairment and Neuroinflammation by Inhibiting the MAPK/NF-κB Pathway in Alzheimer’s Disease: A Multi-Omics Analysis

Marine Drugs, Journal Year: 2025, Volume and Issue: 23(2), P. 74 - 74

Published: Feb. 7, 2025

The rising prevalence of Alzheimer's disease (AD) underscores the urgent need for novel therapeutic agents derived from natural sources. Among flavonoids, 3',4',5,7-tetramethoxyflavone (TMF), a structural analog luteolin, has gained attention its favorable pharmacokinetics and potential neuroprotective properties. Despite significant effects TMF, efficacy mechanism action in AD remain unclear. This study explored TMF's pharmacological models, highlighting ability to improve memory cognitive deficits APP/PS1 mice. TMF reduced Aβ plaques, NFTs formation, glial activation while suppressing neuroinflammation through MAPK/NF-κB pathway. Further analysis LPS-induced BV2 cells revealed reduce microglial activation. These findings highlight anti-neuroinflammatory activity suggesting as treatment AD.

Language: Английский

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Exosomes enriched with miR-124-3p show therapeutic potential in a new microfluidic triculture model that recapitulates neuron–glia crosstalk in Alzheimer’s disease

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 12, 2025

Background Alzheimer’s disease (AD), a complex neurodegenerative associated with ageing, is the leading cause of dementia. Few people early AD are eligible for novel Food and Drug Administration (FDA)-approved drug treatments. Accordingly, new tools diagnosis markers required to predict subtypes, individual stages, most suitable personalized treatment. We previously demonstrated that regulation microRNA (miR)-124 crucial proper neuronal function microglia reshaping in human cell models. Objective The aim this study was develop an efficient miR-124-3p-loaded exosome strategy validate its therapeutic potential using multi-compartment microfluidic device neuron–glia recapitulates age-AD pathological features. Methods results Using cortical from mouse pups, separated glial mixed cultures maintained 2 days vitro (stressed microglia), we tested effects SH-SY5Y-derived exosomes loaded miR-124-3p mimic either by their direct transfection Exo-Fect™ (ET124) or isolation secretome miR-124 transfected cells (CT124). ET124 revealed better delivery effciency higher potent improving stressed status than CT124. Tricultures SH-SY5Y neuroblastoma (SH- WT ) were established presence line (HMC3) immortalized astrocytes (IM-HA) tricompartmentalized devices. Replacement SH- those APP695 SWE tricultures addition low doses hydrogen peroxide used simulate late-onset AD. system mimicked AD-associated neurodegeneration neuroinflammation processes. Notably, exhibited neuroprotective properties across three types model preventing apoptosis neurite deficits, redirecting microglial profiles towards steady state, attenuating inflammatory miRNA fingerprints astrocyte reactivity. Conclusion To best our knowledge, first supporting neuro- immunoprotective miR-124-engineered triculture platform, recapitulating age-related susceptibility Our offers medicines patient subtypes.

Language: Английский

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In silico exploration of Aloe Vera leaf compounds as dual AChE and BChE inhibitors for Alzheimer’s disease therapy

Current Pharmaceutical Analysis, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Advances in Understanding Biomarkers and Treating Neurological Diseases -Role of the Cerebellar Dysfunction and Emerging Therapies

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 102519 - 102519

Published: Sept. 1, 2024

Language: Английский

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