Cited by 291Extracellular vesicles in diseaseNeuroinflammation and Neurodegeneration MechanismsNanoparticle-Based Drug Delivery

Astrocyte-derived extracellular vesicles: Neuroreparative properties and role in the pathogenesis of neurodegenerative disorders

Open access
Upadhya, Raghavendra, Zingg, Winston, Shetty, Siddhant, Shetty, Ashok K.·2020·Journal of Controlled Release

Abstract

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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Crossref · 10.1016/j.jconrel.2020.04.017

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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.

    “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]

    The ‘ADEVs in Alzheimer’s Disease’ section reports that astrocytes exposed to amyloid beta release EVs carrying Aβ42 protofibrils. This supports the claim that EVs from AD-affected brain cells carry disease-associated proteins, but the passage does not establish that the EV-releasing cells are themselves undergoing degeneration; it describes neurotoxicity in neighboring neurons. (LLM, conf=0.82)

    Experimental — accuracy not yet measured
  • EVs serve as potent mediators of intercellular communication by transferring information between cells, including neurons, astrocytes, oligodendrocytes, and microglia.

    “EVs serve as potent mediators of intercellular communication by transferring information between cells, including neurons, astrocytes, oligodendrocytes, and microglia [42, 127, 128] [Fig. 2].”

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3 of the 187 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. [68]Vogel A, Upadhya R, Shetty AK, Neural stem cell derived extracellular vesicles: Attributes and prospects for treating neurodegenerative disorders, EBioMedicine, 38 (2018) 273– 282. 30472088 PMC6306394
  2. [75]Upadhya D, Shetty AK, Promise of extracellular vesicles for diagnosis and treatment of epilepsy, Epilepsy Behav, (2019) 106499. PMC7165061 31636006
  3. [183]Long Q, Upadhya D, Hattiangady B, Kim DK, An SY, Shuai B, Prockop DJ, Shetty AK, Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus, Proc Natl Acad Sci U S A, 114 (2017) E3536– E3545. 28396435 PMC5410779

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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)
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
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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