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Astrocyte-derived extracellular vesicles: Neuroreparative properties and role in the pathogenesis of neurodegenerative disorders
Open accessAbstract
Extracellular vesicles (EVs) released by neural cells play an essential role in brain homeostasis and the crosstalk between neural cells and the periphery. EVs are diverse, nano-sized vesicles, which transport proteins, nucleic acids, and lipids between cells over short and long expanses and hence are proficient for modulating the target cells. EVs released from neural cells are implicated in synaptic plasticity, neuron-glia interface, neuroprotection, neuroregeneration, and the dissemination of neuropathological molecules. This review confers the various properties of EVs secreted by astrocytes and their potential role in health and disease with a focus on evolving concepts. Naïve astrocytes shed EVs containing a host of neuroprotective compounds, which include fibroblast growth factor-2, vascular endothelial growth factor, and apolipoprotein-D. Stimulated astrocytes secrete EVs with neuroprotective molecules including heat shock proteins, synapsin 1, unique microRNAs, and glutamate transporters. Well-characterized astrocyte-derived EVs (ADEVs) generated in specific culture conditions and ADEVs that are engineered to carry the desired miRNAs or proteins are likely useful for treating brain injury and neurogenerative diseases. On the other hand, in conditions such as Alzheimer's disease (AD), stroke, Parkinson's disease, Amyotrophic lateral sclerosis (ALS), and other neuroinflammatory conditions, EVs released by activated astrocytes appear to mediate or exacerbate the pathological processes. The examples include ADEVs spreading the dysregulated complement system in AD, mediating motoneuron toxicity in ALS, and stimulating peripheral leukocyte migration into the brain in inflammatory conditions. Strategies restraining the release of EVs by activated astrocytes or modulating the composition of ADEVs are likely beneficial for treating neurodegenerative diseases. Also, periodic analyses of ADEVs in the blood is useful for detecting astrocyte-specific biomarkers in different neurological conditions and for monitoring disease progression and remission with distinct therapeutic approaches.
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“EVs released from brain cells affected by AD, such as neural cells that undergo degeneration, have been identified to carry pathological proteins associated with the disease [128, 135].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [128]
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“EVs serve as potent mediators of intercellular communication by transferring information between cells, including neurons, astrocytes, oligodendrocytes, and microglia [42, 127, 128] [Fig. 2].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [128]
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“The two-way communication between astrocytes and neurons contributes to the maintenance of brain homeostasis [47].”
From Differential RNA packaging into small extracellular vesicles by neurons and astrocytes (2021) · cites this paper as [47]
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Metadata
- Authors
- Upadhya, R., Zingg, W., Shetty, S., & Shetty, A. K.
- Affiliations
- Texas A&M University (US)
- Corresponding author
- Shetty, Ashok K.
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 323
- Pages
- 225-239
- ISSN
- 0168-3659 (ISSN-L)
- PMC
- PMC7299747
- OpenAlex
- W3015210584
- Cited by
- 282
- References
- 187
- Citations by year
- 2026: 45 · 2025: 54 · 2024: 62 · 2023: 48 · 2022: 39 · 2021: 26 · 2020: 8
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Controlled Release (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, neuroinflammation, complement system, microRNA, astrocyte activation, neuroprotection, biomarkers, traumatic brain injury
- MeSH terms
- Extracellular Vesicles, Alzheimer Disease, Astrocytes, Humans, Neurodegenerative Diseases, Vascular Endothelial Growth Factor A
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