Astrocyte-derived extracellular vesicles: A double-edged sword in central nervous system disorders

Zhao, Shuang; Sheng, Shiyang; Wang, Yi; Ding, Lu; Xu, Xiaonan; Xia, Xiaohuan; Zheng, Jialin

doi:10.1016/j.neubiorev.2021.02.027

Cited by 58 publications

(53 citation statements)

References 125 publications

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“…Experimental results showed that EVs contain some specific molecules, but a great part of their cargo is common [ 84 ]. Worth noting is that astroglial EVs have been called a two-edged sword due to their ability to transfer pathogenic factors in the course of neurodegenerative diseases, aside from their neuro-regenerative potential [ 85 ]. Astrocytes express the soluble NSF attachment protein receptor (SNARE), and its mechanism of action differs from that in neuronal activity (for review see [ 86 ]).…”

Section: How Astrocytes Communicate With Other Cell Typesmentioning

confidence: 99%

Beyond the GFAP-Astrocyte Protein Markers in the Brain

et al. 2021

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The idea of central nervous system as one-man band favoring neurons is long gone. Now we all are aware that neurons and neuroglia are team players and constant communication between those various cell types is essential to maintain functional efficiency and a quick response to danger. Here, we summarize and discuss known and new markers of astroglial multiple functions, their natural heterogeneity, cellular interactions, aging and disease-induced dysfunctions. This review is focused on newly reported facts regarding astrocytes, which are beyond the old stereotypes. We present an up-to-date list of marker proteins used to identify a broad spectrum of astroglial phenotypes related to the various physiological and pathological nervous system conditions. The aim of this review is to help choose markers that are well-tailored for specific needs of further experimental studies, precisely recognizing differential glial phenotypes, or for diagnostic purposes. We hope it will help to categorize the functional and structural diversity of the astroglial population and ease a clear readout of future experimental results.

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Section: How Astrocytes Communicate With Other Cell Typesmentioning

confidence: 99%

Beyond the GFAP-Astrocyte Protein Markers in the Brain

et al. 2021

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“…Moreover, astrocytes may either reverberate activation signaling to microglia, thus promoting their migration towards injury sites and phagocytosis, or inhibit their reactivity when physiological homeostasis is restored [ 1 ]. The exchange of extracellular vesicles containing active molecules, such as mRNA fragments is suggested as an additional mechanism of micro-astroglial interaction: in vitro, extracellular vesicles released by microglia, affect astrocyte expression of reactivity markers and the production of components of the extracellular matrix [ 149 ], whereas vesicles produced by astrocytes modulate microglial migration and phagocytosis [ 150 ]. Among these activities, astrocyte production of ECM molecules, such as fibronectin, represents a further strategy of modulating the microglial immune response.…”

Section: Interactions Between Microglia and Astrocytesmentioning

confidence: 99%

Neuroinflammation: Integrated Nervous Tissue Response through Intercellular Interactions at the “Whole System” Scale

Nosi

Lana

Giovannini

et al. 2021

Cells

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Different cell populations in the nervous tissue establish numerous, heterotypic interactions and perform specific, frequently intersecting activities devoted to the maintenance of homeostasis. Microglia and astrocytes, respectively the immune and the “housekeeper” cells of nervous tissue, play a key role in neurodegenerative diseases. Alterations of tissue homeostasis trigger neuroinflammation, a collective dynamic response of glial cells. Reactive astrocytes and microglia express various functional phenotypes, ranging from anti-inflammatory to pro-inflammatory. Chronic neuroinflammation is characterized by a gradual shift of astroglial and microglial phenotypes from anti-inflammatory to pro-inflammatory, switching their activities from cytoprotective to cytotoxic. In this scenario, the different cell populations reciprocally modulate their phenotypes through intense, reverberating signaling. Current evidence suggests that heterotypic interactions are links in an intricate network of mutual influences and interdependencies connecting all cell types in the nervous system. In this view, activation, modulation, as well as outcomes of neuroinflammation, should be ascribed to the nervous tissue as a whole. While the need remains of identifying further links in this network, a step back to rethink our view of neuroinflammation in the light of the “whole system” scale, could help us to understand some of its most controversial and puzzling features.

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“…Besides myelin-neuron interactions, communication between microglia and astrocytes with neurons modulates neuronal cell death, neurogenesis and synaptic interactions during normal brain development, as well as neuroimmune-responses in various brain diseases [191][192][193]. In particular, secreted extracellular vesicles (EVs) are key players in neuron-glia intercellular signaling and have recently been implicated in the pathogenesis of neurodegenerative disorders [193][194][195]. Distinct profiles of EV miRNAs, derived from neurons and glia, are found in various CNS diseases, often before the onset of irreversible neurological damage.…”

Section: Mirnas In Glial Cells and Glia-neuron Communication Implicated In Brain Diseasesmentioning

confidence: 99%

Multifaceted Regulation of MicroRNA Biogenesis: Essential Roles and Functional Integration in Neuronal and Glial Development

Suster

Feng

2021

IJMS

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MicroRNAs (miRNAs) are small, non-coding RNAs that function as endogenous gene silencers. Soon after the discovery of miRNAs, a subset of brain-enriched and brain-specific miRNAs were identified and significant advancements were made in delineating miRNA function in brain development. However, understanding the molecular mechanisms that regulate miRNA biogenesis in normal and diseased brains has become a prevailing challenge. Besides transcriptional regulation of miRNA host genes, miRNA processing intermediates are subjected to multifaceted regulation by canonical miRNA processing enzymes, RNA binding proteins (RBPs) and epitranscriptomic modifications. Further still, miRNA activity can be regulated by the sponging activity of other non-coding RNA classes, namely circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs). Differential abundance of these factors in neuronal and glial lineages partly underlies the spatiotemporal expression and function of lineage-specific miRNAs. Here, we review the continuously evolving understanding of the regulation of neuronal and glial miRNA biogenesis at the transcriptional and posttranscriptional levels and the cooperativity of miRNA species in targeting key mRNAs to drive lineage-specific development. In addition, we review dysregulation of neuronal and glial miRNAs and the detrimental impacts which contribute to developmental brain disorders.

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Astrocyte-derived extracellular vesicles: A double-edged sword in central nervous system disorders

Cited by 58 publications

References 125 publications

Beyond the GFAP-Astrocyte Protein Markers in the Brain

Beyond the GFAP-Astrocyte Protein Markers in the Brain

Neuroinflammation: Integrated Nervous Tissue Response through Intercellular Interactions at the “Whole System” Scale

Multifaceted Regulation of MicroRNA Biogenesis: Essential Roles and Functional Integration in Neuronal and Glial Development

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