Extracellular vesicles (exosomes and ectosomes) play key roles in the pathology of brain diseases
Open accessAbstract
Last century, neurons and glial cells were mostly believed to play distinct functions, relevant for the brain. Progressively, however, it became clear that neurons, astrocytes and microglia co-operate intensely with each other by release/binding of signaling factors, direct surface binding and generation/release of extracellular vesicles, the exosomes and ectosomes, called together vesicles in this abstract. The present review is focused on these vesicles, fundamental in various brain diseases. Their properties are extraordinary. The specificity of their membrane governs their fusion with distinct target cells, variable depending on the state and specificity of their cells of origin and target. Result of vesicle fusion is the discharge of their cargos into the cytoplasm of target cells. Cargos are composed of critical molecules, from proteins (various nature and function) to nucleotides (especially miRNAs), playing critical roles in immune and neurodegenerative diseases. Among immune diseases is multiple sclerosis, affected by extensive dysregulation of co-trafficking neural and glial vesicles, with distinct miRNAs inducing severe or reducing effects. The vesicle-dependent differences between progressive and relapsing-remitting forms of the disease are relevant for clinical developments. In Alzheimer’s disease the vesicles can affect the brain by changing their generation and inducing co-release of effective proteins, such Aβ and tau, from neurons and astrocytes. Specific miRNAs can delay the long-term development of the disease. Upon their traffic through the blood-brainbarrier, vesicles of various origin reach fluids where they are essential for the identification of biomarkers, important for diagnostic and therapeutic innovations, critical for the future of many brain patients.
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Extracellular tau can be taken up by neighboring cells, both neurons and glial cells, through various pathways including phagocytosis, macropinocytosis, receptor-mediated uptake, endocytosis, and/or membrane fusion of exosomes.
“Meanwhile, the extracellular tau can be taken up by neighboring cells, both neurons and glial cells, through various pathways, including phagocytosis [68], macropinocytosis [69], receptor-mediated uptake [67, 70], endocytosis [71], and/or membrane fusion of exosomes [72, 73].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [72]
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Cited by
Sorted by citations
Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation
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- Authors
- Meldolesi, J.
- Affiliations
- Vita-Salute San Raffaele University (IT)
- Corresponding author
- Meldolesi, Jacopo
- ORCID
- Meldolesi, Jacopo
- Venue
- Molecular Biomedicine
- Published
- 2021-06-20
- Volume
- 2
- Issue
- 1
- Pages
- 18-18
- ISSN
- 2662-8651 (ISSN-L)
- PMC
- PMC8607397
- OpenAlex
- W3176248414
- Cited by
- 47
- References
- 126
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 13 · 2023: 6 · 2022: 9 · 2021: 1
- FWCI
- 0.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Molecular Biomedicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- extracellular vesicles, exosomes, ectosome, brain disorders, neurodegenerative diseases, multiple sclerosis, Alzheimer's disease, microRNA, vesicle fusion, neuron-glia communication, astrocytes, microglia, amyloid-beta, tau protein, blood-brain barrier, biomarkers, relapsing-remitting multiple sclerosis
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