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

Apr 15, 2020Journal of controlled release : official journal of the Controlled Release Society

Brain support cell vesicles: Their role in brain repair and neurodegenerative diseases

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Abstract

Extracellular vesicles (EVs) from neural cells are involved in multiple brain functions and may play a role in various neurological conditions.

EVs are nano-sized vesicles that transport proteins, nucleic acids, and lipids between cells, influencing cell behavior.
Naïve astrocytes release EVs containing neuroprotective compounds such as fibroblast growth factor-2 and vascular endothelial growth factor.
Stimulated astrocytes secrete EVs with neuroprotective molecules, including heat shock proteins and unique microRNAs.
Activated astrocyte-derived EVs may contribute to the progression of diseases like Alzheimer's, Parkinson's, and Amyotrophic lateral sclerosis.
Strategies to modulate the release or content of EVs from activated astrocytes could be beneficial for neurodegenerative disease treatment.
Analyzing astrocyte-derived EVs in blood may help identify specific biomarkers for neurological conditions and track disease progression.

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

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