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, Год журнала: 2025, Номер 16

Опубликована: Март 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.

Язык: Английский

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MiR-4472 serves as a potential biomarker for hypoxic-ischemic encephalopathy and promotes neuronal death as well as hypoxic-ischemic brain damage in neonatal rats by targeting MEF2D

Biochemical and Biophysical Research Communications, Год журнала: 2025, Номер 771, С. 151958 - 151958

Опубликована: Май 5, 2025

Язык: Английский

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Selenium deficiency modulates neonatal pulmonary alveolar development via mitochondrial ROS accumulation and oxidative stress mediated by STAT3 inhibition

Archives of Physiology and Biochemistry, Год журнала: 2025, Номер unknown, С. 1 - 13

Опубликована: Май 14, 2025

Context: Recent findings suggest that Selenium (Se) deficiency in neonates may hinder pulmonary alveolar development, but the underlying molecular mechanisms remain underexplored. Objective: This study utilised a neonatal mouse model to investigate effects of dietary Se on development. Materials and methods: Techniques such as quantitative PCR, Western blotting, immunohistochemistry were employed assess gene protein expression related development oxidative stress markers. Mitochondrial ROS accumulation was quantified using MitoSOX staining, activity sirtuin 3 (STAT3), key transcription factor involved responses, analysed. Results: Our indicate Se-deficient exhibit significantly impaired characterised by reduced number surface area. These structural alterations associated with increased mitochondrial levels stress. Furthermore, resulted decreased STAT3 phosphorylation, suggesting mechanism whereby influences through modulation function. Discussion conclusion: plays critical role modulating dynamics via pathway. The underscores potential supplementation strategic intervention promote maturation prevent disorders neonates. Further research is recommended explore therapeutic thresholds timing administration optimize outcomes.

Язык: Английский

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Molecular Morbidity Score–Can MicroRNAs Assess the Burden of Disease?

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(15), С. 8042 - 8042

Опубликована: Июль 24, 2024

Multimorbidity refers to the presence of two or more chronic diseases and is associated with adverse outcomes for patients. Factors such as an ageing population have contributed a rise in prevalence multimorbidity globally; however, often neglected clinical guidelines. This largely because patients are systematically excluded from trials. Accordingly, there urgent need develop novel biomarkers methods prognostication this cohort The hallmarks now thought potentiate pathogenesis multimorbidity. MicroRNAs small, regulatory, noncoding RNAs which been implicated numerous diseases; substantial body evidence implicating microRNA dysregulation different aetiology diseases. article proposes using framework panel microRNAs assess prognostic burden putative molecular morbidity score would many potential applications, including assessing efficacy interventions, informing decision making facilitating wider inclusion

Язык: Английский

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miR-124 mediates the effects of gut microbial dysbiosis on brain function in chronic stressed mice

Behavioural Brain Research, Год журнала: 2024, Номер 476, С. 115262 - 115262

Опубликована: Сен. 19, 2024

Язык: Английский

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The critical role of miRNA in bacterial zoonosis

International Immunopharmacology, Год журнала: 2024, Номер 143, С. 113267 - 113267

Опубликована: Окт. 6, 2024

Язык: Английский

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