Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease

Cell Metabolism, Год журнала: 2019, Номер 30(4), С. 656 - 673

Опубликована: Авг. 22, 2019

Язык: Английский

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Circulating Extracellular Vesicles in Human Disease

New England Journal of Medicine, Год журнала: 2018, Номер 379(10), С. 958 - 966

Опубликована: Сен. 5, 2018

Interview with Dr. Tushar Patel on the role of extracellular vesicles in physiologic function and as potential biomarkers for disease. (08:09)Download Circulating vesicles, which are produced by normal diseased tissues released into body fluids, can be markers disease processes perhaps even tools to deliver new therapies.

Язык: Английский

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Bidirectional Microglia–Neuron Communication in Health and Disease

Frontiers in Cellular Neuroscience, Год журнала: 2018, Номер 12

Опубликована: Сен. 27, 2018

Microglia are ramified cells that exhibit highly motile processes, which continuously survey the brain parenchyma and react to any insult CNS homeostasis. Although microglia have long been recognized as a crucial player in generating maintaining inflammatory responses CNS, now it has become clear, their function much more diverse, particularly healthy brain. The innate immune response phagocytosis represent only little segment of functional repertoire also includes maintenance biochemical homeostasis, neuronal circuit maturation during development experience- dependent remodeling circuits adult Being equipped by numerous receptors cell surface molecules can perform bidirectional interactions with other types CNS. There is accumulating evidence showing neurons inform about status thus capable controlling microglial activation motility while modulate activities. This review addresses topic: how communicate brain, including fractalkine signaling, secreted soluble factors extracellular vesicles. We summarize current state knowledge physiological role mature further highlight contribution pathologies such Alzheimer's Parkinson's disease, ischemia, traumatic injury, tumour well neuropsychiatric diseases (depression, bipolar disorder schizophrenia).

Язык: Английский

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M2 microglia-derived exosomes protect the mouse brain from ischemia-reperfusion injury via exosomal miR-124

Theranostics, Год журнала: 2019, Номер 9(10), С. 2910 - 2923

Опубликована: Янв. 1, 2019

Rationale: Microglia play a critical role in modulating cell death and neurobehavioral recovery response to brain injury either by direct cell-cell interaction or indirect secretion of trophic factors.Exosomes secreted from cells are well documented deliver bioactive molecules recipient modulate function.Here, we aimed identify whether M2 microglia exert neuroprotection after ischemic attack through an exosome-mediated interaction.Methods: microglia-derived exosomes were intravenously injected into the mouse immediately middle cerebral artery occlusion.Infarct volume, neurological score, neuronal apoptosis examined 3 days attack.Exosome RNA target protein expression levels neurons tissue determined for mechanistic study.Results: Our results showed that taken up vitro vivo.M2 exosome treatment attenuated oxygen-glucose deprivation (p<0.05).In vivo significantly reduced infarct volume behavioral deficits transient ischemia (p<0.05),whereas injection miR-124 knockdown (miR-124k/d) partly reversed neuroprotective effect.Our study further demonstrated ubiquitin-specific protease 14 (USP14) was downstream miR-124.Injection miR-124k/d plus USP14 inhibitor, IU1, achieved comparable effect as alone.Conclusions: We promoted survival via exosomal its USP14.M2 represent promising avenue treating stroke.

Язык: Английский

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Exosome engineering: Current progress in cargo loading and targeted delivery

NanoImpact, Год журнала: 2020, Номер 20, С. 100261 - 100261

Опубликована: Окт. 1, 2020

Exosomes, a class of small bilayer vesicles derived from virtually all eukaryotic cells, have been exploited as promising natural delivery platform due to their low toxicity, excellent structural stability, nanoscale size, cargo loading ability, and editable surface structure. To load therapeutic or diagnostic cargos (drugs, nucleic acids, proteins, peptides, nanomaterials) into exosomes, multiple techniques developed, such incubating with exosomes exosome-secreting transfection, physical treatments (sonication, electroporation, extrusion, freeze-thaw, surfactant treatment, dialysis), in situ synthesis. Moreover, homing-molecules high receptor binding affinity, acidic milieu responsiveness, magnetic properties assembled on exosomal by transfection chemical modification, conferring the targeting capacity exosomes. In this review, we summarize biogenesis, contents functions provide comprehensive discussion for strategies membrane modification targeted delivery.

Язык: Английский

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Cell-to-cell Communication by Extracellular Vesicles: Focus on Microglia

Neuroscience, Год журнала: 2018, Номер 405, С. 148 - 157

Опубликована: Апрель 14, 2018

Extracellular vesicles, including exosomes and microvesicles, are small, nano-to-micrometer vesicles that released from cells. While initially observed in immune cells reticulocytes as meant to remove archaic proteins, now they have been almost all cell types of multicellular organisms. Growing evidence indicates extracellular containing lipids, proteins RNAs, represent an efficient way transfer functional cargoes one another. In the central nervous system, extensive cross-talk ongoing between neurons glia, microglia, brain, takes advantage secreted which mediate intercellular communication over long range distance. Recent literature supports a critical role for mediating complex coordinated among neurons, astrocytes both healthy diseased brain. this review, we focus on biogenesis function microglia-related their putative Alzheimer's disease pathology.

Язык: Английский

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Neuroinflammation as a target for treatment of stroke using mesenchymal stem cells and extracellular vesicles

Journal of Neuroinflammation, Год журнала: 2019, Номер 16(1)

Опубликована: Сен. 12, 2019

Abstract Ischemic stroke is the third cause of death in developed countries and main reason severe disability. Brain ischemia leads to production damage-associated molecular patterns (DAMPs) by neurons glial cells which results astrocyte microglia activation, pro-inflammatory cytokines chemokines production, blood-brain barrier (BBB) disruption, infiltration leukocytes from peripheral blood into infarcted area, further exacerbation tissue damage. However, some immune such as or monocytes are capable change their phenotype anti-inflammatory, produce anti-inflammatory cytokines, protect injured nervous tissue. In this situation, therapies, will modulate response after brain ischemia, transplantation mesenchymal stem (MSCs) catching interest. Many experimental studies ischemic revealed that MSCs able act neuroprotective, through stimulation neurogenesis, oligodendrogenesis, astrogenesis, angiogenesis. may also have an ability replace cells, but release paracrine factors directly environment via extracellular vesicles (EVs) seems play most pronounced role. EVs membrane structures containing proteins, lipids, nucleic acids, they express similar properties derived. lower immunogenicity, do not risk vessel blockage, capacity cross barrier. Experimental showed immunomodulatory neuroprotective properties; therefore, can stimulate neurogenesis Up now, 20 clinical trials with MSC patients were performed, two concerned on only hemorrhagic 13 studied stroke. There no trial EV injection so far, case miR-124-enriched administration planned probably there be more near future.

Язык: Английский

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MicroRNA-based therapeutics in central nervous system injuries

Journal of Cerebral Blood Flow & Metabolism, Год журнала: 2018, Номер 38(7), С. 1125 - 1148

Опубликована: Апрель 30, 2018

Central nervous system (CNS) injuries, such as stroke, traumatic brain injury (TBI) and spinal cord (SCI), are important causes of death long-term disability worldwide. MicroRNA (miRNA), small non-coding RNA molecules that negatively regulate gene expression, can serve diagnostic biomarkers emerging novel therapeutic targets for CNS injuries. MiRNA-based therapeutics include miRNA mimics inhibitors (antagomiRs) to respectively decrease increase the expression target genes. In this review, we summarize current miRNA-based applications in TBI SCI. Administration methods, time windows dosage effective delivery drugs into discussed. The underlying mechanisms reviewed including oxidative stress, inflammation, apoptosis, blood-brain barrier protection, angiogenesis neurogenesis. Pharmacological agents protect against injuries by targeting specific miRNAs presented along with challenges potential therapies.

Язык: Английский

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Exosomes in inflammation and role as biomarkers

Clinica Chimica Acta, Год журнала: 2018, Номер 488, С. 165 - 171

Опубликована: Ноя. 9, 2018

Язык: Английский

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Role of Exosomes in Central Nervous System Diseases

Frontiers in Molecular Neuroscience, Год журнала: 2019, Номер 12

Опубликована: Окт. 4, 2019

There are many types of intercellular communication, and extracellular vesicles one the important forms this. They released by a variety cell types, heterogeneous, can roughly be divided into microvesicles exosomes according to their occurrence function. Of course, do not just play role in cell-to-cell communication. In nervous system, participate maintain myelin sheath, eliminate waste. Similarly, brain central system diseases, such as stroke, Alzheimer's disease (AD), Parkinson's (PD), prion disease, traumatic encephalopathy (CTE), with both positive negative effects (such transfer misfolded proteins). Exosomes contain key bioactive substances therefore considered snapshot intracellular environment. Studies have shown that from found cerebrospinal fluid peripheral body fluids, contents will change occurrence. Because penetrate blood barrier (BBB) highly stable circulation, they protect disease-related molecules well therefore, using biomarker diseases is an attractive prospect used monitor development enable early diagnosis treatment optimization. this review, we discuss current state knowledge exosomes, introduce pathophysiological roles different applications viable pathological biomarker.

Язык: Английский

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