ArticleAging cell2023
Exosomal miR-532-5p induced by long-term exercise rescues blood-brain barrier function in 5XFAD mice via downregulation of EPHA4.
Article in Aging cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- The impact of physical exercise on neuroinflammation mechanism in Alzheimer's disease.Frontiers in aging neuroscience · 2024Pooled it
- Treatment of animal models of Alzheimer's disease with extracellular vesicles or exosomes and involvement of microRNAs.Neural regeneration research · 2026Article
- Review
- Peripheral and Central miRNA Signatures in Alzheimer's Disease: Tissue-Specific Variability, Sex-Associated Differences, and Implications for Blood-Based Biomarkers.International journal of molecular sciences · 2026Review
- MicroRNA and Alzheimer's disease: Diagnostic biomarkers and potential therapeutic targets.Neural regeneration research · 2026Article
- Study on Regulatory Mechanism ofMolecules (Basel, Switzerland) · 2026Article
- Exercise‑induced extracellular vesicle microRNA regulates physiological function (Review).Molecular medicine reports · 2026Review
- Serum EphA4 is Associated with both Parenchymal Hematoma and Increased Blood-Brain Barrier Permeability after Ischemic Stroke.Neurocritical care · 2026Article
- Extracellular Vesicles in Tauopathies: Mechanisms and Applications.International journal of molecular sciences · 2026Review
- Exercise-derived exosomes: molecular mediators of systemic health and disease therapy.Journal of nanobiotechnology · 2026Review
- Exercise-conditioned extracellular vesicles in Alzheimer's disease: a multi-organ signaling network linking peripheral adaptation to brain pathology.Frontiers in immunology · 2026Review
- Extracellular vesicle therapeutics in Alzheimer's disease: mechanisms, progress, and prospects.Extracellular vesicles and circulating nucleic acids · 2026Review
- Article
- Exercise attenuates the hallmarks of aging: Novel perspectives.Journal of sport and health science · 2025Review
- Expert consensus statement for basic research of animal exercise intervention studies in chronic disease prevention and treatment: A joint position paper of the Exercise Science branch of the Biophysical Society of China and the Metabolism and Genetics branch of the Genetics Society of China.Journal of sport and health science · 2025Article
- High-intensity interval training improves cognitive dysfunction in chronically stressed mice through alleviating homocysteine-induced transcriptional repression ofNeurobiology of stress · 2025Article
- DP1 Receptor Blockade Attenuates Microglial Senescence and Cognitive Decline Caused by PTGDS in Exosomes From Aged Brains.Aging cell · 2025Article
- Inhibition of miR-4284 could reduce apoptosis and neuroinflammation by targeting APBA1/JAK1/STAT3 signaling in Alzheimer's disease.Cell & bioscience · 2025Article
- Long-Term Treadmill Exercise and Voluntary Running Pre-Training Attenuates Vascular Dementia-Related Pathology by Regulating Hippocampal Structural Synaptic Plasticity in a Rat Model.Brain and behavior · 2025Article
- Childhood resolution of early abnormal miRNA following neonatal encephalopathy.Scientific reports · 2025Observational
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The breakdown of the blood-brain barrier, which develops early in Alzheimer's disease (AD), contributes to cognitive impairment. Exercise not only reduces the risk factors for AD but also confers direct protection against cognitive decline. However, the exact molecular mechanisms remain elusive, particularly whether exercise can liberate the function of the blood-brain barrier. Here, we demonstrate that long-term exercise promotes the clearance of brain amyloid-β by improving the function of the blood-brain barrier in 5XFAD mice. Significantly, treating primary brain pericytes or endothelial cells with exosomes isolated from the brain of exercised 5XFAD mice improves cell proliferation and upregulates PDGFRβ, ZO-1, and claudin-5. Moreover, exosomes isolated from exercised mice exhibit significant changes in miR-532-5p. Administration or transfection of miR-532-5p to sedentary mice or primary brain pericytes and endothelial cells reproduces the improvement of blood-brain barrier function. Exosomal miR-532-5p targets EPHA4, and accordingly, expression of EphA4 is decreased in exercised mice and miR-532-5p overexpressed mice. A specific siRNA targeting EPHA4 recapitulates the effects on blood-brain barrier-associated cells observed in exercised 5XFAD mice. Overall, our findings suggest that exosomes released by the brain contain a specific miRNA that is altered by exercise and has an impact on blood-brain barrier function in AD.
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