ArticleCellular and molecular life sciences : CMLS2023
Differential intracellular trafficking of extracellular vesicles in microglia and astrocytes.
Article in Cellular and molecular life sciences : CMLS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- A Novel Reporter Mouse for Astrocyte-Derived Extracellular Vesicles Reveals Enrichment of Cargo at Neuronal Mitochondria.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Hippocampal neural stem cell-derived extracellular vesicles modulate microglia to promote resilience against tau oligomers.Neural regeneration research · 2026Article
- Human Platelet-Derived Extracellular Vesicles Are Internalized by Human Induced Pluripotent Stem Cell-Derived Neurons Under Control and Hypoxic Conditions.Journal of extracellular biology · 2026Article
- Biology and therapeutic potential of extracellular vesicle targeting and uptake.Nature reviews. Molecular cell biology · 2026Review
- A novel reporter mouse for astrocyte-derived extracellular vesicles reveals trafficking of cargo to neuronal mitochondria.bioRxiv : the preprint server for biology · 2026Article
- Hyaluronic Acid Decoration Facilitates CD44-Mediated Targeting and Alters Protein Corona Formation of Extracellular Vesicles.Journal of extracellular vesicles · 2026Article
- Olfactory ensheathing cells exosomes enhance neurological recovery in brain-injured rats by modulating Nrf2-ferroptosis pathway.Bioengineering & translational medicine · 2026Article
- Bioreactor expansion of human neural progenitor cells for exosome scalable production and miRNA-engineering.Journal of biological engineering · 2026Article
- Microvesicle Profiles in Patients with HIV, HBV, and HCV Infections: An Exploratory Pilot Study.Microorganisms · 2026Article
- Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026Review
- Exploring the Spatial Limits of Extracellular Vesicles-Mediated Intercellular Communication.Journal of extracellular vesicles · 2025Article
- Lipidomic and proteomic insights from extracellular vesicles in the postmortem dorsolateral prefrontal cortex reveal substance use disorder-induced brain changes.Translational psychiatry · 2025Article
- The Multifaceted Role of Extracellular Vesicles in Alzheimer's Disease.Journal of neurochemistry · 2025Review
- Stem cell-derived extracellular vesicles: novel therapeutics for cerebral injury following cardiac arrest and potential mechanisms.Cell & bioscience · 2025Review
- Extracellular vesicles in TDP-43 proteinopathies: pathogenesis and biomarker potential.Molecular neurodegeneration · 2025Review
- Toxoplasma gondii infection of neurons alters the production and content of extracellular vesicles directing astrocyte phenotype and contributing to the loss of GLT-1 in the infected brain.PLoS pathogens · 2025Article
- Cold vs. Room Temperature: A Comparative Analysis of Platelet Functionality in Cold Storage.Biomedicines · 2025Article
- Neuroprotective Proteins in Hypoxia-stressed Astrocyte-Derived Extracellular Vesicles.Current neuropharmacology · 2025Article
- Mesenchymal stem cell-derived extracellular vesicles: current advances in preparation and therapeutic applications for neurological disorders.Frontiers in cell and developmental biology · 2025Review
- Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Extracellular vesicles (EVs) have emerged as key players in cell-to-cell communication in both physiological and pathological processes in the Central Nervous System. Thus far, the intracellular pathways involved in uptake and trafficking of EVs within different cell types of the brain are poorly understood. In our study, the endocytic processes and subcellular sorting of EVs were investigated in primary glial cells, particularly linked with the EV-associated α-synuclein (α-syn) transmission. Mouse microglia and astrocytic primary cultures were incubated with DiI-stained mouse brain-derived EVs. The internalization and trafficking pathways were analyzed in cells treated with pharmacological reagents that block the major endocytic pathways. Brain-derived EVs were internalized by both glial cell types; however, uptake was more efficient in microglia than in astrocytes. Colocalization of EVs with early and late endocytic markers (Rab5, Lamp1) indicated that EVs are sorted to endo-lysosomes for subsequent processing. Blocking actin-dependent phagocytosis and/or macropinocytosis with Cytochalasin D or EIPA inhibited EV entry into glial cells, whereas treatment with inhibitors that strip cholesterol off the plasma membrane, induced uptake, however differentially altered endosomal sorting. EV-associated fibrillar α-Syn was efficiently internalized and detected in Rab5- and Lamp1-positive compartments within microglia. Our study strongly suggests that EVs enter glial cells through phagocytosis and/or macropinocytosis and are sorted to endo-lysosomes for subsequent processing. Further, brain-derived EVs serve as scavengers and mediate cell-to-glia transfer of pathological α-Syn which is also targeted to the endolysosomal pathway, suggesting a beneficial role in microglia-mediated clearance of toxic protein aggregates, present in numerous neurodegenerative diseases.
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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.