Neuron‐derived extracellular vesicles contain synaptic proteins, promote spine formation, activate TrkB‐mediated signalling and preserve neuronal complexity

Journal of Extracellular Vesicles, Journal Year: 2023, Volume and Issue: 12(9)

Published: Sept. 1, 2023

Extracellular vesicles (EVs) play an important role in intercellular communication as carriers of signalling molecules such bioactive miRNAs, proteins and lipids. EVs are key players the functioning central nervous system (CNS) by influencing synaptic events modulating recipient neurons. However, specific neuron-to-neuron via is still not well understood. Here, we provide evidence that primary neurons uptake neuron-derived soma, dendrites, even dendritic spines, carry proteins. Neuron-derived increased spine density promoted phosphorylation Akt ribosomal protein S6 (RPS6), TrkB-signalling, without impairing neuronal network activity. Strikingly, exerted a trophic effect on challenged nutrient-deprived Altogether, our results place spotlight for plasticity modulation possible therapeutic tool to fight neurodegeneration.

Language: Английский

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Extracellular Vesicles as Mediators of Neuroinflammation in Intercellular and Inter-Organ Crosstalk

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7041 - 7041

Published: June 27, 2024

Neuroinflammation, crucial in neurological disorders like Alzheimer's disease, multiple sclerosis, and hepatic encephalopathy, involves complex immune responses. Extracellular vesicles (EVs) play a pivotal role intercellular inter-organ communication, influencing disease progression. EVs serve as key mediators the system, containing molecules capable of activating molecular pathways that exacerbate neuroinflammatory processes disorders. However, from mesenchymal stem cells show promise reducing neuroinflammation cognitive deficits. can cross CNS barriers, peripheral signals influence brain function via EV-mediated impacting barrier Understanding EV interactions within other organs could unveil novel therapeutic targets for

Language: Английский

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Smart Nanoscale Extracellular Vesicles in the Brain: Unveiling their Biology, Diagnostic Potential, and Therapeutic Applications

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(6), P. 6709 - 6742

Published: Feb. 5, 2024

Information exchange is essential for the brain, where it communicates physiological and pathological signals to periphery vice versa. Extracellular vesicles (EVs) are a heterogeneous group of membrane-bound cellular informants actively transferring informative calls from brain via lipids, proteins, nucleic acid cargos. In recent years, EVs have also been widely used understand function, given their "cell-like" properties. On one hand, presence neuron astrocyte-derived in biological fluids exploited as biomarkers mechanisms progression multiple neurological disorders; on other, designing targeted therapies due potential cross blood-brain-barrier (BBB). Despite expanding literature context central nervous system (CNS) physiology related disorders, comprehensive compilation existing knowledge still needs be made available. current review, we provide detailed insight into multifaceted role brain-derived extracellular (BDEVs) intricate regulation physiology. Our focus extends significance these spectrum including tumors, neurodegenerative conditions, neuropsychiatric diseases, autoimmune others. Throughout parallels drawn using various evaluating utility early detection monitoring. Additionally, discuss promising prospects utilizing therapy while acknowledging limitations challenges associated with applications clinical scenarios. A foundational comprehension state-of-the-art EV research informing design future studies.

Language: Английский

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Mesenchymal stem cell-derived extracellular vesicles: A novel promising neuroprotective agent for Alzheimer's disease

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 222, P. 116064 - 116064

Published: Feb. 17, 2024

Language: Английский

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Notch receptor-ligand binding facilitates extracellular vesicle-mediated neuron-to-neuron communication

Cell Reports, Journal Year: 2024, Volume and Issue: 43(2), P. 113680 - 113680

Published: Jan. 21, 2024

Extracellular vesicles (EVs) facilitate intercellular communication by transferring cargo between cells in a variety of tissues. However, how EVs achieve cell-type-specific is still largely unknown. We found that Notch1 and Notch2 proteins are expressed on the surface neuronal have been generated response to excitatory synaptic activity. Notch ligands bind these plasma membrane, trigger their internalization, activate signaling pathway, drive expression target genes. The generation requires endosomal sorting complex required for transport-associated protein Alix. Adult Alix conditional knockout mice reduced hippocampal activation glutamatergic expression. Thus, neuron-to-neuron via receptor-ligand system brain.

Language: Английский

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Extracellular particles: emerging insights into central nervous system diseases

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 1, 2025

Extracellular particles (EPs), including extracellular vesicles (EVs) and non-vesicular (NVEPs), are multimolecular biomaterials released by cells that play a crucial role in intercellular communication. Recently, new subtypes of EPs associated with central nervous system (CNS), such as exophers supermeres have been identified. These provide perspectives for understanding the pathological progression CNS disorders confer potential diagnostic value liquid biopsies neurodegenerative diseases (NDs). Moreover, emerged promising drug delivery vehicles targeted platforms CNS-specific therapies. In this review, we delineate landscape EP their roles pathophysiology diseases. We also review recent advances EP-based diagnosis NDs highlight importance analytical single-particle resolution exploitation biomarkers. Furthermore, summarize application engineered EVs treatment outline underexplored NVEPs novel therapeutic agents.

Language: Английский

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Extracellular vesicle-derived silk fibroin nanoparticles loaded with MFGE8 accelerate skin ulcer healing by targeting the vascular endothelial cells

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 29, 2023

Reduced supplies of oxygen and nutrients caused by vascular injury lead to difficult-to-heal pressure ulcers (PU) in clinical practice. Rapid repair the skin wound is key resolution this challenge, but measures are still limited. We described beneficial effects extracellular vesicle-derived silk fibroin nanoparticles (NPs) loaded with milk fat globule EGF factor 8 (MFGE8) on accelerating blood vessel PU healing targeting CD13 endothelial cells (VECs).CD13, specific protein NGR, MFGE8, an inhibitor ferroptosis, were detected VECs tissues. Then, NPs synthesized via fibroin, MFGE8-coated (NPs@MFGE8) assembled loading purified MFGE8 produced Chinese hamster ovary cells. Lentivirus was used over-express obtained MFGE8-engineered vesicles (EVs-MFGE8) secreted these VECs. The inhibitory effect EVs-MFGE8 or NPs@MFGE8 ferroptosis vitro. NGR peptide cross-linked into NGR-NPs@MFGE8. Collagen synthesize fibroin/collagen hydrogel. After being NGR-NPs@MFGE8, hydrogel sustained-release carrier investigate vivo.MFGE8 decreased, increased Similar inhibiting could inhibit mitochondrial autophagy-induced Compared hydrogels NPs@MFGE8, NGR-NPs@MFGE8 consistently released VECs, thereby autophagy hypoxia effectively rats.The great significance use as a dressing tissues, preventing formation promoting healing.

Language: Английский

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Hitting the target: cell signaling pathways modulation by extracellular vesicles

Extracellular Vesicles and Circulating Nucleic Acids, Journal Year: 2024, Volume and Issue: 5(3), P. 627 - 52

Published: Sept. 24, 2024

Extracellular vesicles (EVs) are lipid bilayer-enclosed nanoparticles released outside the cell. EVs have drawn attention not only for their role in cell waste disposal, but also as additional tools cell-to-cell communication. Their complex contents include lipids, proteins, nucleic acids (RNA, DNA), and metabolites. A large part of these molecules involved mediating or influencing signal transduction target cells. In multicellular organisms, been suggested to modulate signals cells localized either neighboring tissue distant regions body by interacting with surface entering via endocytosis membrane fusion. Most EV-modulated signaling pathways considerable because they affect morphogenetic pathways, well activated cytokines growth factors. Therefore, implicated relevant biological processes, such embryonic development, cancer initiation spreading, differentiation repair, immune response. Furthermore, it has recently emerged that organisms interact receive through microbiota edible plants. This review reports studies investigating EV-mediated mammalian cells, a focus on key organism organ homeostasis,

Language: Английский

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Blood-derived APLP1 ⁺ extracellular vesicles are potential biomarkers for the early diagnosis of brain diseases

Science Advances, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 1, 2025

The early detection of neurodegenerative diseases necessitates the identification specific brain-derived biomolecules in peripheral blood. In this context, our investigation delineates role amyloid precursor-like protein 1 (APLP1)—a predominantly localized oligodendrocytes and neurons—as a previously unidentified biomarker extracellular vesicles (EVs). Through rigorous analysis, APLP1 + EVs from human sera were unequivocally determined to be cerebral origin. This assertion was corroborated by distinctive small RNA expression patterns EVs. miRNAs’ putative targets within these manifested pronounced brain, fortifying their neurospecific provenance. We subjected findings stringent validation using Thy-1 GFP M line mice, transgenic models wherein is confined hippocampal neurons. An amalgamation results with an exhaustive data analysis accentuates potential as cerebrally originated biomarkers. Synthesizing findings, are postulated not merely diagnostic markers but seminal entities shaping future trajectory disease diagnostics.

Language: Английский

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Small Extracellular Vesicles Promote Axon Outgrowth by Engaging the Wnt-Planar Cell Polarity Pathway

Cells, Journal Year: 2025, Volume and Issue: 14(1), P. 56 - 56

Published: Jan. 6, 2025

In neurons, the acquisition of a polarized morphology is achieved upon outgrowth single axon from one several neurites. Small extracellular vesicles (sEVs), such as exosomes, diverse sources are known to promote neurite and thus may have therapeutic potential. However, effect fibroblast-derived exosomes on elongation in neurons central nervous system under growth-permissive conditions remains unclear. Here, we show that sEVs neuronal mouse primary embryonic cortical neurons. Mechanistically, demonstrate sEV-induced increase requires endogenous Wnts core PCP components including Prickle, Vangl, Frizzled, Dishevelled. We internalized by colocalize with Wnt7b, induce relocalization Vangl2 distal during outgrowth. contrast, derived or astrocytes do not outgrowth, while activated inhibit elongation. Thus, our data reveal through Wnt-PCP pathway manner dependent Wnts.

Language: Английский

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