ArticleJournal of molecular neuroscience : MN2021
Lipopolysaccharide-Induced Exosomal miR-146a Is Involved in Altered Expression of Alzheimer's Risk Genes Via Suppression of TLR4 Signaling.
Article in Journal of molecular neuroscience : MN, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Engineered mesenchymal stem cell-derived extracellular vesicles overexpressing miR-146a alleviate neuroinflammation in Alzheimer's disease.Neural regeneration research · 2026Article
- MicroRNA and Alzheimer's disease: Diagnostic biomarkers and potential therapeutic targets.Neural regeneration research · 2026Article
- Review
- Exosomes in Alzheimer's disease: neuroinflammation mitigation via immune modulation and inflammatory pathway targeting.Molecular biology reports · 2026Review
- Tissue-Derived Small Extracellular Vesicles: Emerging Regulators of Inter-Organ Crosstalk in Health and Disease.Metabolites · 2026Review
- Neuroinflammation in Alzheimer's disease: glial crosstalk, pathological modulation, and therapeutic implications.Frontiers in immunology · 2026Review
- Infection-driven gut dysbiosis and epigenetic programming of microglia: toward a systems level framework linking microbial metabolites, neuroinflammation, synaptic dysfunction, and probiotic modulation.Frontiers in cellular and infection microbiology · 2026Review
- Extracellular vesicles for macrophage reprogramming: an emerging paradigm in immunomodulatory therapeutics.Journal of biological engineering · 2025Review
- Beyond inflammation: a comprehensive microglial regulation model in chronic pain.Molecular biology reports · 2025Review
- The role of exosomes in immunopathology and potential therapeutic implications.Cellular & molecular immunology · 2025Review
- Exosomal microRNAs in common mental disorders: Mechanisms, biomarker potential and therapeutic implications.World journal of psychiatry · 2025Review
- Exosomal non-coding RNAs: gatekeepers of inflammation in autoimmune disease.Journal of inflammation (London, England) · 2025Review
- [Recent advances on the role of exosomes in neurodegenerative diseases].Se pu = Chinese journal of chromatography · 2025Review
- MnTheranostics · 2025Article
- Review
- Gut microbiota metabolites: potential therapeutic targets for Alzheimer's disease?Frontiers in pharmacology · 2024Review
- Comparative Insight into Microglia/Macrophages-Associated Pathways in Glioblastoma and Alzheimer's Disease.International journal of molecular sciences · 2023Review
- The emerging role of exosomes in communication between the periphery and the central nervous system.MedComm · 2023Review
- Early activation of Toll-like receptor-3 reduces the pathological progression of Alzheimer's disease in APP/PS1 mouse.Alzheimer's research & therapy · 2023Article
- Non-Coding RNA in Microglia Activation and Neuroinflammation in Alzheimer's Disease.Journal of inflammation research · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Repeated exposure to toll-like receptor 4 (TLR4) ligands, such as lipopolysaccharide (LPS), reduces responses of monocytes/macrophages to LPS (LPS/endotoxin tolerance). Microglial exposure to Aβ deposits, a TLR4 ligand, may cause "Aβ/LPS tolerance," leading to decreased Aβ clearance. We demonstrated that microglial activation by LPS is diminished in Aβ deposit-bearing 12-month-old model mice of Alzheimer's disease (AD), compared with non-AD mice and Aβ deposit-free 2-month-old AD mice. Because miR-146a plays a predominant role in inducing TLR tolerance in macrophages and because miR-146a in extracellular vesicles (EVs) shed by inflammatory macrophages increases in circulation, we investigated potential roles of miR-146a and inflammatory EVs in inducing TLR tolerance in microglia and in altering expression of inflammatory AD risk genes. We found that miR-146a upregulation induces TLR tolerance and alters expression of inflammatory AD risk genes in response to LPS treatment in BV2 microglia. LPS brain injection altered expression of the AD risk genes in 12-month-old AD mice but not in non-AD littermates. EVs from inflammatory macrophages polarize BV2 microglia to M1 phenotype and induce TLR tolerance. Microglia exposed to Aβ in the brain show reduced cytokine responses to systemic inflammation due to peripheral LPS injection, indicating TLR/Aβ tolerance in microglia. Our results suggest that increased miR-146a induces microglial Aβ/LPS tolerance and that circulating EVs shed by inflammatory macrophages contribute to microglial Aβ/LPS tolerance, leading to reduced Aβ clearance. Our study also suggests that altered expression of inflammatory AD risk genes may contribute to AD development via the same molecular mechanism underlying LPS tolerance.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.