<scp>T</scp>he roles of extracellular vesicle micro<scp>RNA</scp>s in the central nervous system

Blandford, Stephanie N.; Galloway, Dylan A.; Moore, Craig S.

doi:10.1002/glia.23445

Cited by 51 publications

(30 citation statements)

References 125 publications

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“…In contrast to GJs and TNTs, the encapsulation of miRNA into exosomes allows intercellular transport across long distances without direct cell‐cell contacts. A plenty of studies have proven the exosome mediated functional shuttling of miRNA in multiple cell types . For example, the uptake of miR‐222‐3p enriched exosomes by macrophages, released from ovarian cancer cells, led to stimulation of the STAT3 pathway which in turn promotes macrophage activation .…”

Section: Alternative Routes For Intercellular Mirna Exchangementioning

confidence: 99%

Potential mechanisms of microRNA mobility

Lemcke

Dávid

2018

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microRNAs (miRNAs) are important epigenetic modulators of gene expression that control cellular physiology as well as tissue homeostasis, and development. In addition to the temporal aspects of miRNA-mediated gene regulation, the intracellular localization of miRNA is crucial for its silencing activity. Recent studies indicated that miRNA is even translocated between cells via gap junctional cell-cell contacts, allowing spatiotemporal modulation of gene expression within multicellular systems. Although non coding RNA remains a focus of intense research, studies regarding the intra-and intercellular mobility of small RNAs are still largely missing. Emerging data from experimental and computational work suggest the involvement of transport mechanisms governing proper localization of miRNA in single cells and cellular syncytia. Based on these data, we discuss a model of miRNA translocation that could help to address the spatial aspects of miRNA function and the impact of miRNA molecules on the intercellular signaling network.

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Section: Alternative Routes For Intercellular Mirna Exchangementioning

confidence: 99%

Potential mechanisms of microRNA mobility

Lemcke

Dávid

2018

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“…Many reports have shown that miRNAs are released from the cells in the extracellular environment through exosomes. Recent studies have shown that exosomal cargo of cellular proteins, lipids, and miRNAs act as mediators of intercellular crosstalk between the effector and recipient cells [9]. Their ability to protect cargo contents from degradation and traverse across the intact BBB to reach the circulation highlights their importance as potential disease biomarkers [10].…”

Section: Introductionmentioning

confidence: 99%

Exosomal MicroRNAs Released by Activated Astrocytes as Potential Neuroinflammatory Biomarkers

Gayen

Bhomia

Balakathiresan

et al. 2020

IJMS

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Neuroinflammation is a hallmark of several neurodegenerative diseases and disorders, including traumatic brain injury (TBI). Neuroinflammation results in the activation of glial cells which exacerbates the neuroinflammatory process by secretion of pro-inflammatory cytokines and results in disruption of glial transmission networks. The glial cells, including astrocytes, play a critical role in the maintenance of homeostasis in the brain. Activated astrocytes release several factors as part of the inflammatory process including cytokines, proteins, and microRNAs (miRNAs). MiRNAs are noncoding RNA molecules involved in normal physiological processes and disease pathogenesis. MiRNAs have been implicated as important cell signaling molecules, and they are potential diagnostic biomarkers and therapeutic targets for various diseases, including neurological disorders. Exosomal miRNAs released by astrocytic response to neuroinflammation is not yet studied. In this study, primary human astrocytes were activated by IL-1β stimulation and we examined astrocytic exosomal miRNA cargo released in a neuroinflammatory stress model. Results indicate that acute neuroinflammation and oxidative stress induced by IL-1β generates the release of a specific subset of miRNAs via exosomes, which may have a potential role in regulating the inflammatory response. Additionally, these miRNAs may serve as potential biomarkers of neuroinflammation associated with neurological disorders and injuries.

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“…44,45 A key characteristic of EVs is their ability to penetrate the blood-brain barrier and release related RNAs and proteins into the central nervous system. 46 Studies have shown that MSCs-EVs can exert neuroprotective effects by promoting the growth and repair of blood vessels, repairing and regenerating nerve cells, and inhibiting apoptosis of nerve cells after stroke. 47 Studies have shown that EVs can stimulate the growth of nerve cells, 48 induce neuronal proliferation, 49 increase the number of axons, 50 regulate the peripheral immune response, 51 reduce the area of infarction after cerebral ischemia, improve brain function, 12 and promote axonal growth and white matter recovery.…”

Section: Discussionmentioning

confidence: 99%

<p>Neuroprotective Effect of Mesenchymal Stromal Cell-Derived Extracellular Vesicles Against Cerebral Ischemia-Reperfusion-Induced Neural Functional Injury: A Pivotal Role for AMPK and JAK2/STAT3/NF-κB Signaling Pathway Modulation</p>

Han¹,

Cao²,

Xue³

et al. 2020

DDDT

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Introduction: Cerebral ischemia-reperfusion injury (CIRI) is the main factor that leads to poor prognosis of cerebral ischemia. Apoptosis has been shown to occur during the process of CIRI. Extracellular vesicles derived from mesenchymal stromal cells (MSCs-EVs) have shown broad potential for treating brain dysfunction and eliciting neuroprotective effects after stroke through neurogenesis and angiogenesis. However, the mechanism of action of extracellular vesicles during CIRI is not well known. Methods: A middle cerebral artery occlusion (MCAO) model was induced by the modified Longa method, and MSCs-EVs were injected via the tail vein. Results: Our results showed that MSCs-EVs significantly alleviated neurological deficits, reduced the volume of cerebral infarction and brain water content, improved pathological lesions in cortical brain tissue, and attenuated neuronal apoptosis in the cortex at 24 h and 48 h after MCAO in rats. Western blotting analysis showed that MSCs-EVs significantly upregulated p-AMPK and downregulated p-JAK2, p-STAT3 and p-NF-κB. In addition, an AMPK pathway blocker reversed the effect of MSCs-EVs on brain damage. Conclusion: These results indicate that MSCs-EVs protected MCAO-injured rats, possibly by regulating the AMPK and JAK2/STAT3/NF-κB signaling pathways. This study supports the use of MSCs-EVs as a potential treatment strategy for MCAO in the future.

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The roles of extracellular vesicle microRNAs in the central nervous system

Cited by 51 publications

References 125 publications

Potential mechanisms of microRNA mobility

Potential mechanisms of microRNA mobility

Exosomal MicroRNAs Released by Activated Astrocytes as Potential Neuroinflammatory Biomarkers

<p>Neuroprotective Effect of Mesenchymal Stromal Cell-Derived Extracellular Vesicles Against Cerebral Ischemia-Reperfusion-Induced Neural Functional Injury: A Pivotal Role for AMPK and JAK2/STAT3/NF-κB Signaling Pathway Modulation</p>

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