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1

Maire, Cecile, Amanda Salviano-Silva, Katharina Kolbe, Manfred Westphal, Katrin Lamszus, and Franz Ricklefs. "TMIC-64. EXTRACELLULAR VESICLE TRAFFICKING IN GBM." Neuro-Oncology 24, Supplement_7 (2022): vii285—vii286. http://dx.doi.org/10.1093/neuonc/noac209.1108.

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Abstract Extracellular vesicles (EVs) are secreted by all cell types, including tumor cells, and are found in increased numbers in the plasma of GBM patients. EVs may contain high-value genetic material that can be useful for tracking tumor development, as well as membrane proteins that affect other cells. This prompted us to investigate how tumor EVs might influence immune cells in glioma, and in primary and secondary lymphoid organs as well as in the circulation. To this end we used a syngeneic GBM mouse model and tracked tumor EVs from the brain to the meninges, cervical lymph nodes, plasma
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Kumar, Prashant, Fahad Zadjali, Ying Yao, et al. "Single Gene Mutations in Pkd1 or Tsc2 Alter Extracellular Vesicle Production and Trafficking." Biology 11, no. 5 (2022): 709. http://dx.doi.org/10.3390/biology11050709.

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Patients with autosomal dominant polycystic kidney disease (ADPKD) and tuberous sclerosis complex (TSC) are born with normal or near-normal kidneys that later develop cysts and prematurely lose function. Both renal cystic diseases appear to be mediated, at least in part, by disease-promoting extracellular vesicles (EVs) that induce genetically intact cells to participate in the renal disease process. We used centrifugation and size exclusion chromatography to isolate the EVs for study. We characterized the EVs using tunable resistive pulse sensing, dynamic light scattering, transmission electr
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Santamaria, Sara, Maria Cristina Gagliani, Grazia Bellese, et al. "Imaging of Endocytic Trafficking and Extracellular Vesicles Released Under Neratinib Treatment in ERBB2+ Breast Cancer Cells." Journal of Histochemistry & Cytochemistry 69, no. 7 (2021): 461–73. http://dx.doi.org/10.1369/00221554211026297.

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Breast cancers (BCa) with ERBB2 amplification show rapid tumor growth, increased disease progression, and lower survival rate. Deregulated intracellular trafficking and extracellular vesicle (EVs) release are mechanisms that support cancer progression and resistance to treatments. Neratinib (NE) is a Food and Drug Administration–approved pan-ERBB inhibitor employed for the treatment of ERBB2+ BCa that blocks signaling and causes survival inhibition. However, the effects of NE on ERBB2 internalization, its trafficking to multivesicular bodies (MVBs), and the release of EVs that originate from t
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Baxter, Amy A. "Stoking the Fire: How Dying Cells Propagate Inflammatory Signalling through Extracellular Vesicle Trafficking." International Journal of Molecular Sciences 21, no. 19 (2020): 7256. http://dx.doi.org/10.3390/ijms21197256.

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Communication between dying cells and their environment is a critical process that promotes tissue homeostasis during normal cellular turnover, whilst during disease settings, it can contribute to inflammation through the release of intracellular factors. Extracellular vesicles (EVs) are a heterogeneous class of membrane-bound cell-derived structures that can engage in intercellular communication via the trafficking of bioactive molecules between cells and tissues. In addition to the well-described functions of EVs derived from living cells, the ability of dying cells to release EVs capable of
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Roberts-Dalton, H. D., A. Cocks, J. M. Falcon-Perez, et al. "Fluorescence labelling of extracellular vesicles using a novel thiol-based strategy for quantitative analysis of cellular delivery and intracellular traffic." Nanoscale 9, no. 36 (2017): 13693–706. http://dx.doi.org/10.1039/c7nr04128d.

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Ortega, Miguel A., Oscar Fraile-Martinez, Cielo Garcia-Montero, et al. "An Updated View of the Importance of Vesicular Trafficking and Transport and Their Role in Immune-Mediated Diseases: Potential Therapeutic Interventions." Membranes 12, no. 6 (2022): 552. http://dx.doi.org/10.3390/membranes12060552.

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Cellular trafficking is the set of processes of distributing different macromolecules by the cell. This process is highly regulated in cells, involving a system of organelles (endomembranous system), among which are a great variety of vesicles that can be secreted from the cell, giving rise to different types of extracellular vesicles (EVs) that can be captured by other cells to modulate their function. The cells of the immune system are especially sensitive to this cellular traffic, producing and releasing different classes of EVs, especially in disease states. There is growing interest in th
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Cruz Camacho, Abel, Daniel Alfandari, Ewa Kozela, and Neta Regev-Rudzki. "Biogenesis of extracellular vesicles in protozoan parasites: The ESCRT complex in the trafficking fast lane?" PLOS Pathogens 19, no. 2 (2023): e1011140. http://dx.doi.org/10.1371/journal.ppat.1011140.

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Extracellular vesicles (EVs) provide a central mechanism of cell–cell communication. While EVs are found in most organisms, their pathogenesis-promoting roles in parasites are of particular interest given the potential for medical insight and consequential therapeutic intervention. Yet, a key feature of EVs in human parasitic protozoa remains elusive: their mechanisms of biogenesis. Here, we survey the current knowledge on the biogenesis pathways of EVs secreted by the four main clades of human parasitic protozoa: apicomplexans, trypanosomatids, flagellates, and amoebae. In particular, we shin
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Zhang, Pan, Su Bin Lim, Kuan Jiang, Ti Weng Chew, Boon Chuan Low, and Chwee Teck Lim. "Distinct mRNAs in Cancer Extracellular Vesicles Activate Angiogenesis and Alter Transcriptome of Vascular Endothelial Cells." Cancers 13, no. 9 (2021): 2009. http://dx.doi.org/10.3390/cancers13092009.

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Cancer-derived extracellular vesicles (EVs) have been demonstrated to be implicated in various processes of cancer development, with most of the EV-induced changes attributed to EV-proteins and EV-microRNAs. However, the knowledge about the abundance of cancer EV-mRNAs and their contribution to cancer development remain elusive. Here, we show that mRNAs prevail in cancer EVs as compared with normal EVs, and cancer EVs that carry abundant angiogenic mRNAs activate angiogenesis in human umbilical vein endothelial cells (HUVECs). Specifically, of a gene panel comprising 61 hypoxia-targeted oncoge
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Auger, Clément, Aude Brunel, Tiffany Darbas, et al. "Extracellular Vesicle Measurements with Nanoparticle Tracking Analysis: A Different Appreciation of Up and Down Secretion." International Journal of Molecular Sciences 23, no. 4 (2022): 2310. http://dx.doi.org/10.3390/ijms23042310.

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As is the case with most eucaryotic cells, cancer cells are able to secrete extracellular vesicles (EVs) as a communication means towards their environment and surrounding cells. EVs are represented by microvesicles and smaller vesicles called exosomes, which are known for their involvement in cancer aggressiveness. The release of such EVs requires the intervention of trafficking-associated proteins, mostly represented by the RAB-GTPases family. In particular, RAB27A is known for its role in addressing EVs-to-be secreted towards the the plasma membrane. In this study, shRNAs targeting RAB27A w
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Lipinski, Simone, and Katharina Tiemann. "Extracellular Vesicles and Their Role in the Spatial and Temporal Expansion of Tumor–Immune Interactions." International Journal of Molecular Sciences 22, no. 7 (2021): 3374. http://dx.doi.org/10.3390/ijms22073374.

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Extracellular vesicles (EVs) serve as trafficking vehicles and intercellular communication tools. Their cargo molecules directly reflect characteristics of their parental cell. This includes information on cell identity and specific cellular conditions, ranging from normal to pathological states. In cancer, the content of EVs derived from tumor cells is altered and can induce oncogenic reprogramming of target cells. As a result, tumor-derived EVs compromise antitumor immunity and promote cancer progression and spreading. However, this pro-oncogenic phenotype is constantly being challenged by E
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11

Picca, Anna, Flora Guerra, Riccardo Calvani, et al. "Mitochondrial Dysfunction and Aging: Insights from the Analysis of Extracellular Vesicles." International Journal of Molecular Sciences 20, no. 4 (2019): 805. http://dx.doi.org/10.3390/ijms20040805.

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The progressive decline of cell function and integrity, manifesting clinically as increased vulnerability to adverse outcomes and death, is core to biological aging. Mitochondrial dysfunction, oxidative stress, altered intercellular communication (including chronic low-grade inflammation), genomic instability, telomere attrition, loss of proteostasis, altered nutrient sensing, epigenetic alterations, and stem cell exhaustion have been proposed as hallmarks of aging. These “aging pillars” are not mutually exclusive, making the matter intricate and leaving numerous unanswered questions. The char
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Abdelhamed, Sherif, Noah I. Hornick, and Peter Kurre. "Residual HSPC in the Leukemia Microenvironment Are Reprogrammed Via Extracellular Vesicle Trafficking." Blood 128, no. 22 (2016): 888. http://dx.doi.org/10.1182/blood.v128.22.888.888.

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Several groups have shown that leukemic cells create a self-reinforcing bone marrow (BM) niche that functionally impairs normal hematopoietic stem and progenitor cells (HSPC) indirectly through stroma-secreted factors. We recently demonstrated an alternative mechanism whereby extracellular vesicles (EVs) from acute myeloid leukemia (AML) patients and cell lines, but not BM CD34 controls, suppress their clonogenicity through EV trafficking of microRNA that directly downregulate critical transcription factors (c-Myb and HoxA9). Here, we aimed to clarify the fate of residual HSPC in in vivo AML x
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Yamamoto, Satoshi, Kohji Okamura, Risa Fujii, et al. "Specimen-specific drift of densities defines distinct subclasses of extracellular vesicles from human whole saliva." PLOS ONE 16, no. 4 (2021): e0249526. http://dx.doi.org/10.1371/journal.pone.0249526.

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Extracellular vesicles (EVs) in body fluids constitute heterogenous populations, which mirror their diverse parental cells as well as distinct EV-generation pathways. Various methodologies have been proposed to differentiate EVs in order to deepen the current understanding of EV biology. Equilibrium density-gradient centrifugation has often been used to separate EVs based on their buoyant densities; however, the standard conditions used for the method do not necessarily allow all EVs to move to their equilibrium density positions, which complicates the categorization of EVs. Here, by prolongin
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Sawaged, Savannah, Thomas Mota, Honit Piplani, et al. "TBK1 and GABARAP family members suppress Coxsackievirus B infection by limiting viral production and promoting autophagic degradation of viral extracellular vesicles." PLOS Pathogens 18, no. 8 (2022): e1010350. http://dx.doi.org/10.1371/journal.ppat.1010350.

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Host-pathogen dynamics are constantly at play during enteroviral infection. Coxsackievirus B (CVB) is a common juvenile enterovirus that infects multiple organs and drives inflammatory diseases including acute pancreatitis and myocarditis. Much like other enteroviruses, CVB is capable of manipulating host machinery to hijack and subvert autophagy for its benefit. We have previously reported that CVB triggers the release of infectious extracellular vesicles (EVs) which originate from autophagosomes. These EVs facilitate efficient dissemination of infectious virus. Here, we report that TBK1 (Tan
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15

Kwok, Zhi Hao, Chenghao Wang, and Yang Jin. "Extracellular Vesicle Transportation and Uptake by Recipient Cells: A Critical Process to Regulate Human Diseases." Processes 9, no. 2 (2021): 273. http://dx.doi.org/10.3390/pr9020273.

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Emerging evidence highlights the relevance of extracellular vesicles (EVs) in modulating human diseases including but not limited to cancer, inflammation, and neurological disorders. EVs can be found in almost all types of human body fluids, suggesting that their trafficking may allow for their targeting to remote recipient cells. While molecular processes underlying EV biogenesis and secretion are increasingly elucidated, mechanisms governing EV transportation, target finding and binding, as well as uptake into recipient cells remain to be characterized. Understanding the specificity of EV tr
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16

Di Rocco, Giuliana, Silvia Baldari, and Gabriele Toietta. "Towards Therapeutic Delivery of Extracellular Vesicles: Strategies forIn VivoTracking and Biodistribution Analysis." Stem Cells International 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/5029619.

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Extracellular vesicles (EVs), such as microvesicles and exosomes, are membranous structures containing bioactive material released by several cells types, including mesenchymal stem/stromal cells (MSCs). Increasing lines of evidences point to EVs as paracrine mediators of the beneficial effects on tissue remodeling associated with cell therapy. Administration of MSCs-derived EVs has therefore the potential to open new and safer therapeutic avenues, alternative to cell-based approaches, for degenerative diseases. However, an enhanced knowledge aboutin vivoEVs trafficking upon delivery is requir
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17

Bitencourt, Tamires A., André M. Pessoni, Bianca T. M. Oliveira, Lysangela R. Alves, and Fausto Almeida. "The RNA Content of Fungal Extracellular Vesicles: At the “Cutting-Edge” of Pathophysiology Regulation." Cells 11, no. 14 (2022): 2184. http://dx.doi.org/10.3390/cells11142184.

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The role of extracellular vesicles (EVs) in interkingdom communication is widely accepted, and their role in intraspecies communication has been strengthened by recent research. Based on the regulation promoted by EV-associated molecules, the interactions between host and pathogens can reveal different pathways that ultimately affect infection outcomes. As a great part of the regulation is ascribable to RNA contained in EVs, many studies have focused on profiling RNAs in fungal and host EVs, tracking their accumulation during infection, and identifying potential target genes. Herein, we overvi
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Soares, Maria, Maria M. Pinto, Rui Jorge Nobre, et al. "Isolation of Extracellular Vesicles from Human Follicular Fluid: Size-Exclusion Chromatography versus Ultracentrifugation." Biomolecules 13, no. 2 (2023): 278. http://dx.doi.org/10.3390/biom13020278.

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Follicular fluid (FF) is the microenvironment where a growing oocyte develops. Intrafollicular communication ensures oocyte competence and is carried out through paracrine signaling, the exchange of molecules via gap junctions, and the trafficking of extracellular vesicles (EVs). The study of FF-derived EVs is important for both translational and fundamental research in the female reproductive field. This study aimed to compare the efficacy and purity of two EV isolation methods: size-exclusion chromatography (SEC) and ultracentrifugation (UC). EVs isolated using SEC and UC were compared regar
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Tse, Shun Wilford, Chee Fan Tan, Jung Eun Park, et al. "Microenvironmental Hypoxia Induces Dynamic Changes in Lung Cancer Synthesis and Secretion of Extracellular Vesicles." Cancers 12, no. 10 (2020): 2917. http://dx.doi.org/10.3390/cancers12102917.

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Extracellular vesicles (EVs) mediate critical intercellular communication within healthy tissues, but are also exploited by tumour cells to promote angiogenesis, metastasis, and host immunosuppression under hypoxic stress. We hypothesize that hypoxic tumours synthesize hypoxia-sensitive proteins for packing into EVs to modulate their microenvironment for cancer progression. In the current report, we employed a heavy isotope pulse/trace quantitative proteomic approach to study hypoxia sensitive proteins in tumour-derived EVs protein. The results revealed that hypoxia stimulated cells to synthes
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Auger, Clément, Niki Christou, Aude Brunel, Aurélie Perraud, and Mireille Verdier. "Autophagy and Extracellular Vesicles in Colorectal Cancer: Interactions and Common Actors?" Cancers 13, no. 5 (2021): 1039. http://dx.doi.org/10.3390/cancers13051039.

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Autophagy is a homeostatic process involved in the degradation of disabled proteins and organelles using lysosomes. This mechanism requires the recruitment of specialized proteins for vesicle trafficking, that may also be involved in other types of machinery such as the biogenesis and secretion of extracellular vesicles (EVs), and particularly small EVs called exosomes. Among these proteins, Rab-GTPases may operate in both pathways, thus representing an interesting avenue for further study regarding the interaction between autophagy and extracellular vesicle machinery. Both mechanisms are invo
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Willysson, Annie, Anne-lie Ståhl, Daniel Gillet, et al. "Shiga Toxin Uptake and Sequestration in Extracellular Vesicles Is Mediated by Its B-Subunit." Toxins 12, no. 7 (2020): 449. http://dx.doi.org/10.3390/toxins12070449.

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Shiga toxin (Stx)-stimulated blood cells shed extracellular vesicles (EVs) which can transfer the toxin to the kidneys and lead to hemolytic uremic syndrome. The toxin can be taken up by renal cells within EVs wherein the toxin is released, ultimately leading to cell death. The mechanism by which Stx is taken up, translocated, and sequestered in EVs was addressed in this study utilizing the B-subunit that binds to the globotriaosylceramide (Gb3) receptor. We found that Stx1B was released in EVs within minutes after stimulation of HeLa cells or red blood cells, detected by live cell imaging and
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McCluskey, Gavin, Karen E. Morrison, Colette Donaghy, Frederique Rene, William Duddy, and Stephanie Duguez. "Extracellular Vesicles in Amyotrophic Lateral Sclerosis." Life 13, no. 1 (2022): 121. http://dx.doi.org/10.3390/life13010121.

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Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disease and is the most common adult motor neuron disease. The disease pathogenesis is complex with the perturbation of multiple pathways proposed, including mitochondrial dysfunction, RNA processing, glutamate excitotoxicity, endoplasmic reticulum stress, protein homeostasis and endosomal transport/extracellular vesicle (EV) secretion. EVs are nanoscopic membrane-bound particles that are released from cells, involved in the intercellular communication of proteins, lipids and genetic material, and there is increasing evidence of
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Brunel, Aude, Gaëlle Bégaud, Clément Auger, et al. "Autophagy and Extracellular Vesicles, Connected to rabGTPase Family, Support Aggressiveness in Cancer Stem Cells." Cells 10, no. 6 (2021): 1330. http://dx.doi.org/10.3390/cells10061330.

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Even though cancers have been widely studied and real advances in therapeutic care have been made in the last few decades, relapses are still frequently observed, often due to therapeutic resistance. Cancer Stem Cells (CSCs) are, in part, responsible for this resistance. They are able to survive harsh conditions such as hypoxia or nutrient deprivation. Autophagy and Extracellular Vesicles (EVs) secretion are cellular processes that help CSC survival. Autophagy is a recycling process and EVs secretion is essential for cell-to-cell communication. Their roles in stemness maintenance have been wel
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Zanetti-Domingues, Laura C., Scott E. Bonner, R. Sumanth Iyer, Marisa L. Martin-Fernandez, and Veronica Huber. "Cooperation and Interplay between EGFR Signalling and Extracellular Vesicle Biogenesis in Cancer." Cells 9, no. 12 (2020): 2639. http://dx.doi.org/10.3390/cells9122639.

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Epidermal growth factor receptor (EGFR) takes centre stage in carcinogenesis throughout its entire cellular trafficking odyssey. When loaded in extracellular vesicles (EVs), EGFR is one of the key proteins involved in the transfer of information between parental cancer and bystander cells in the tumour microenvironment. To hijack EVs, EGFR needs to play multiple signalling roles in the life cycle of EVs. The receptor is involved in the biogenesis of specific EV subpopulations, it signals as an active cargo, and it can influence the uptake of EVs by recipient cells. EGFR regulates its own inclu
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Khanna, Kanika, Sukhmeen Kaur Kohli, Vinod Kumar, et al. "Multiple Facets of Plant-Microbiome Associations in Unlocking the Communication Paradigm through Extracellular Vesicles." Current Protein & Peptide Science 22, no. 12 (2021): 848–72. http://dx.doi.org/10.2174/1389203722666211109101140.

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: Communication among different species across kingdoms occurs through a chain of regulatory molecules that are transferred around cellular boundaries. These molecules are also crucial for defense, virulence, and pathogenesis. In the past, the transport of proteins in long distance communication was observed, but in the present era, the discovery of extracellular vesicles (EVs) has changed our understanding of molecular communication. EVs are not only involved in cell signaling and immunity but also can transfer information by sRNAs, forming a basis for interactions among a wide variety of org
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Catani, Lucia, Michele Cavo, and Francesca Palandri. "The Power of Extracellular Vesicles in Myeloproliferative Neoplasms: “Crafting” a Microenvironment That Matters." Cells 10, no. 9 (2021): 2316. http://dx.doi.org/10.3390/cells10092316.

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Myeloproliferative Neoplasms (MPN) are acquired clonal disorders of the hematopoietic stem cells and include Essential Thrombocythemia, Polycythemia Vera and Myelofibrosis. MPN are characterized by mutations in three driver genes (JAK2, CALR and MPL) and by a state of chronic inflammation. Notably, MPN patients experience increased risk of thrombosis, disease progression, second neoplasia and evolution to acute leukemia. Extracellular vesicles (EVs) are a heterogeneous population of microparticles with a role in cell-cell communication. The EV-mediated cross-talk occurs via the trafficking of
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Wąchalska, Magda, Michał Rychłowski, Kinga Grabowska, et al. "Palmitoylated mNeonGreen Protein as a Tool for Visualization and Uptake Studies of Extracellular Vesicles." Membranes 10, no. 12 (2020): 373. http://dx.doi.org/10.3390/membranes10120373.

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Extracellular vesicles (EVs) are membranous nanoparticles released by cells as vital mediators of intercellular communication. As such, EVs have become an attractive target for pathogens and cancer cells, which can take control over their cargo composition, as well as their trafficking, shaping the pathogenesis. Despite almost four decades of research on EVs, the number of specific and efficient EV labeling methods is limited, and there is still no universal method for the visualization of their transport in living cells. Lipophilic dyes that non-specifically intercalate into the EVs membranes
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Charreau, Béatrice. "Secretome and Tunneling Nanotubes: A Multilevel Network for Long Range Intercellular Communication between Endothelial Cells and Distant Cells." International Journal of Molecular Sciences 22, no. 15 (2021): 7971. http://dx.doi.org/10.3390/ijms22157971.

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As a cellular interface between the blood and tissues, the endothelial cell (EC) monolayer is involved in the control of key functions including vascular tone, permeability and homeostasis, leucocyte trafficking and hemostasis. EC regulatory functions require long-distance communications between ECs, circulating hematopoietic cells and other vascular cells for efficient adjusting thrombosis, angiogenesis, inflammation, infection and immunity. This intercellular crosstalk operates through the extracellular space and is orchestrated in part by the secretory pathway and the exocytosis of Weibel P
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Maguire, Julie E., Malan Silva, Ken C. Q. Nguyen, et al. "Myristoylated CIL-7 regulates ciliary extracellular vesicle biogenesis." Molecular Biology of the Cell 26, no. 15 (2015): 2823–32. http://dx.doi.org/10.1091/mbc.e15-01-0009.

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The cilium both releases and binds to extracellular vesicles (EVs). EVs may be used by cells as a form of intercellular communication and mediate a broad range of physiological and pathological processes. The mammalian polycystins (PCs) localize to cilia, as well as to urinary EVs released from renal epithelial cells. PC ciliary trafficking defects may be an underlying cause of autosomal dominant polycystic kidney disease (PKD), and ciliary–EV interactions have been proposed to play a central role in the biology of PKD. In Caenorhabditis elegans and mammals, PC1 and PC2 act in the same genetic
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Tang, Yunhui, Katie Groom, Larry Chamley, and Qi Chen. "Melatonin, a Potential Therapeutic Agent for Preeclampsia, Reduces the Extrusion of Toxic Extracellular Vesicles from Preeclamptic Placentae." Cells 10, no. 8 (2021): 1904. http://dx.doi.org/10.3390/cells10081904.

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Preeclampsia, characterised by maternal endothelial cell activation, is triggered by toxic factors, such as placental extracellular vesicles (EVs) from a dysfunctional placenta. The increased oxidative stress seen in the preeclamptic placenta links to endoplasmic reticulum (ER) stress. The ER regulates protein folding and trafficking. When the ER is stressed, proteins are misfolded, and misfolded proteins are toxic. Misfolded proteins can be exported from cells, via EVs which target to other cells where the misfolded proteins may also be toxic. Melatonin is a hormone and antioxidant produced b
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Savage, John, Ciaran Manus Maguire, and Adrielle Prina-Mello. "Origins to Outcomes: A Role for Extracellular Vesicles in Precision Medicine." Precision Nanomedicine 1, no. 1 (2018): 18–42. http://dx.doi.org/10.29016/180419.1.

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Extracellular vesicles (EVs) are of great interest in biological research, and though they are a relatively recent discovery, they have rapidly shown great potential for use in clinical applications. The various techniques used in EV isolation along with their respective strengths, weaknesses, and potential for downstream applications are outlined here. A brief description of the different approaches in exosome characterisation are subsequently described. It has been highlighted that despite the recent developments in these processes, there is still a great deal of refinement to be made. EVs a
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Walsh, Jonathon D., Juan Wang, Molly DeHart, Inna A. Nikonorova, Jagan Srinivasan, and Maureen M. Barr. "Tracking N- and C-termini of C. elegans polycystin-1 reveals their distinct targeting requirements and functions in cilia and extracellular vesicles." PLOS Genetics 18, no. 12 (2022): e1010560. http://dx.doi.org/10.1371/journal.pgen.1010560.

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The cilium acts as an antenna receiving and sending signals, the latter via extracellular vesicles (EVs). In C. elegans and mammals, the Autosomal Dominant Polycystic Kidney Disease (ADPKD) gene products polycystin-1 (PC1) and polycystin-2 (PC2) localize to both cilia and EVs, act in the same genetic pathway, and function in a sensory capacity, suggesting ancient conservation. However, the functions of the polycystins on cilia and EVs remain enigmatic. We used our C. elegans model and endogenously fluorescent-tagged LOV-1/polycystin-1 to study LOV-1 processing, trafficking, transport, EV bioge
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Subramanian, Subbaya, Xianda Zhao, and Ce Yaun. "Tumor exosome mediated immune regulation in colorectal cancer." Journal of Immunology 202, no. 1_Supplement (2019): 194.15. http://dx.doi.org/10.4049/jimmunol.202.supp.194.15.

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Abstract Colorectal cancer (CRC) remains the third most common cause of cancer-related deaths in the United States. Most (~85%) of CRC tumors are nonimmunogenic, i.e. they lack a significant number of tumor-infiltrating T cells, and are typically unresponsive to the current immune checkpoint inhibitor-based therapies. T cells isolated from nonimmunogenic, microsatellite stable (MSS) CRC have lower levels of CD28, which provides a costimulatory signal required for T-cell activation, trafficking, proliferation, differentiation, and cytotoxic activity. CRC tumors have elevated levels of miR-503 a
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Cerri, Silvia, Cristina Ghezzi, Gerardo Ongari, et al. "GBA Mutations Influence the Release and Pathological Effects of Small Extracellular Vesicles from Fibroblasts of Patients with Parkinson’s Disease." International Journal of Molecular Sciences 22, no. 4 (2021): 2215. http://dx.doi.org/10.3390/ijms22042215.

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Heterozygous mutations in the GBA gene, encoding the lysosomal enzyme glucocerebrosidase (GCase), are the strongest known genetic risk factor for Parkinson’s disease (PD). The molecular mechanisms underlying the increased PD risk and the variable phenotypes observed in carriers of different GBA mutations are not yet fully elucidated. Extracellular vesicles (EVs) have gained increasing importance in neurodegenerative diseases since they can vehiculate pathological molecules potentially promoting disease propagation. Accumulating evidence showed that perturbations of the endosomal–lysosomal path
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Sanwald, Julia L., Gereon Poschmann, Kai Stühler, Christian Behrends, Silke Hoffmann, and Dieter Willbold. "The GABARAP Co-Secretome Identified by APEX2-GABARAP Proximity Labelling of Extracellular Vesicles." Cells 9, no. 6 (2020): 1468. http://dx.doi.org/10.3390/cells9061468.

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The autophagy-related ATG8 protein GABARAP has not only been shown to be involved in the cellular self-degradation process called autophagy but also fulfils functions in intracellular trafficking processes such as receptor transport to the plasma membrane. Notably, available mass spectrometry data suggest that GABARAP is also secreted into extracellular vesicles (EVs). Here, we confirm this finding by the immunoblotting of EVs isolated from cell culture supernatants and human blood serum using specific anti-GABARAP antibodies. To investigate the mechanism by which GABARAP is secreted, we appli
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Alves, Sara, Joana Pereira, Rupert Mayer, et al. "Cells Responding to Closely Related Cholesterol-Dependent Cytolysins Release Extracellular Vesicles with a Common Proteomic Content Including Membrane Repair Proteins." Toxins 15, no. 1 (2022): 4. http://dx.doi.org/10.3390/toxins15010004.

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The plasma membrane (PM) protects cells from extracellular threats and supports cellular homeostasis. Some pathogens produce pore-forming toxins (PFTs) that disrupt PM integrity by forming transmembrane pores. High PFT concentrations cause massive damage leading to cell death and facilitating infection. Sub-lytic PFT doses activate repair mechanisms to restore PM integrity, support cell survival and limit disease. Shedding of extracellular vesicles (EVs) has been proposed as a key mechanism to eliminate PFT pores and restore PM integrity. We show here that cholesterol-dependent cytolysins (CDC
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37

Ipinmoroti, Ayodeji O., Brennetta J. Crenshaw, Rachana Pandit, Sanjay Kumar, Brian Sims, and Qiana L. Matthews. "Human Adenovirus Serotype 3 Infection Modulates the Biogenesis and Composition of Lung Cell-Derived Extracellular Vesicles." Journal of Immunology Research 2021 (December 9, 2021): 1–19. http://dx.doi.org/10.1155/2021/2958394.

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Adenovirus (Ad) is a major causal agent of acute respiratory infections. However, they are a powerful delivery system for gene therapy and vaccines. Some Ad serotypes antagonize the immune system leading to meningitis, conjunctivitis, gastroenteritis, and/or acute hemorrhagic cystitis. Studies have shown that the release of small, membrane-derived extracellular vesicles (EVs) may offer a mechanism by which viruses can enter cells via receptor-independent entry and how they influence disease pathogenesis and/or host protection considering their existence in almost all bodily fluids. We proposed
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38

Peruzzotti-Jametti, Luca, Joshua D. Bernstock, Cory M. Willis, et al. "Neural stem cells traffic functional mitochondria via extracellular vesicles." PLOS Biology 19, no. 4 (2021): e3001166. http://dx.doi.org/10.1371/journal.pbio.3001166.

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Neural stem cell (NSC) transplantation induces recovery in animal models of central nervous system (CNS) diseases. Although the replacement of lost endogenous cells was originally proposed as the primary healing mechanism of NSC grafts, it is now clear that transplanted NSCs operate via multiple mechanisms, including the horizontal exchange of therapeutic cargoes to host cells via extracellular vesicles (EVs). EVs are membrane particles trafficking nucleic acids, proteins, metabolites and metabolic enzymes, lipids, and entire organelles. However, the function and the contribution of these carg
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39

Carvalho, Ana Sofia, Henrique Baeta, Andreia F. A. Henriques, et al. "Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping." International Journal of Molecular Sciences 22, no. 20 (2021): 11004. http://dx.doi.org/10.3390/ijms222011004.

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The role of extracellular vesicles (EVs) proteome in diffuse large B-cell lymphoma (DLBCL) pathology, subclassification, and patient screening is unexplored. We analyzed by state-of-the-art mass spectrometry the whole cell and secreted extracellular vesicles (EVs) proteomes of different molecular subtypes of DLBCL, germinal center B cell (GCB subtype), and activated B cell (ABC subtype). After quality control assessment, we compared whole-cell and secreted EVs proteomes of the two cell-of-origin (COO) categories, GCB and ABC subtypes, resulting in 288/1115 significantly differential expressed
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40

Jewett, Kathryn A., Ruth E. Thomas, Chi Q. Phan, et al. "Glucocerebrosidase reduces the spread of protein aggregation in a Drosophila melanogaster model of neurodegeneration by regulating proteins trafficked by extracellular vesicles." PLOS Genetics 17, no. 2 (2021): e1008859. http://dx.doi.org/10.1371/journal.pgen.1008859.

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Abnormal protein aggregation within neurons is a key pathologic feature of Parkinson’s disease (PD). The spread of brain protein aggregates is associated with clinical disease progression, but how this occurs remains unclear. Mutations in glucosidase, beta acid 1 (GBA), which encodes glucocerebrosidase (GCase), are the most penetrant common genetic risk factor for PD and dementia with Lewy bodies and associate with faster disease progression. To explore how GBA mutations influence pathogenesis, we previously created a Drosophila model of GBA deficiency (Gba1b) that manifests neurodegeneration
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41

Beer, Katharina B., Jennifer Rivas-Castillo, Kenneth Kuhn, et al. "Extracellular vesicle budding is inhibited by redundant regulators of TAT-5 flippase localization and phospholipid asymmetry." Proceedings of the National Academy of Sciences 115, no. 6 (2018): E1127—E1136. http://dx.doi.org/10.1073/pnas.1714085115.

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Cells release extracellular vesicles (EVs) that mediate intercellular communication and repair damaged membranes. Despite the pleiotropic functions of EVs in vitro, their in vivo function is debated, largely because it is unclear how to induce or inhibit their formation. In particular, the mechanisms of EV release by plasma membrane budding or ectocytosis are poorly understood. We previously showed that TAT-5 phospholipid flippase activity maintains the asymmetric localization of the lipid phosphatidylethanolamine (PE) in the plasma membrane and inhibits EV budding by ectocytosis in Caenorhabd
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42

Spinelli, Cristiana, Lata Adnani, Dongsic Choi, and Janusz Rak. "Extracellular Vesicles as Conduits of Non-Coding RNA Emission and Intercellular Transfer in Brain Tumors." Non-Coding RNA 5, no. 1 (2018): 1. http://dx.doi.org/10.3390/ncrna5010001.

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Non-coding RNA (ncRNA) species have emerged in as molecular fingerprints and regulators of brain tumor pathogenesis and progression. While changes in ncRNA levels have been traditionally regarded as cell intrinsic there is mounting evidence for their extracellular and paracrine function. One of the key mechanisms that enables ncRNA to exit from cells is their selective packaging into extracellular vesicles (EVs), and trafficking in the extracellular space and biofluids. Vesicular export processes reduce intracellular levels of specific ncRNA in EV donor cells while creating a pool of EV-associ
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Chen, Ding-Wen, Seul Jung, Jian-Meng Fan, et al. "Microrna-155 Trafficking Incites Compartmental Inflammation in the Leukemic Niche." Blood 136, Supplement 1 (2020): 36. http://dx.doi.org/10.1182/blood-2020-137758.

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Compartmental bone marrow (BM) inflammation has been linked to acute myeloid leukemia (AML) progression and hematopoietic dysfunction, yet the underlying mechanisms remain unclear. MicroRNAs (miRs) are capable of broadly deregulating cellular gene expression programs through simultaneous, dose-dependent action on a panel of target genes. MicroRNA-155, a widely known proinflammatory miRNA is overexpressed in AML patients, in particular those with Flt3-ITD. We recently observed that miR-155 is highly abundant in AML patient plasma-derived extracellular vesicles (AML-EV) and identified inflammati
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44

Ouweneel, Amber B., Michael J. Thomas, and Mary G. Sorci-Thomas. "The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes." Journal of Lipid Research 61, no. 5 (2019): 676–86. http://dx.doi.org/10.1194/jlr.tr119000383.

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Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM bu
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Lovisa, Federica, Anna Garbin, Sara Crotti, et al. "Increased Tenascin C, Osteopontin and HSP90 Levels in Plasmatic Small Extracellular Vesicles of Pediatric ALK-Positive Anaplastic Large Cell Lymphoma: New Prognostic Biomarkers?" Diagnostics 11, no. 2 (2021): 253. http://dx.doi.org/10.3390/diagnostics11020253.

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Over the past 15 years, several biological and pathological characteristics proved their significance in pediatric anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL) prognostic stratification. However, the identification of new non-invasive disease biomarkers, relying on the most important disease mechanisms, is still necessary. In recent years, plasmatic circulating small extracellular vesicles (S-EVs) gathered great importance both as stable biomarker carriers and active players in tumorigenesis. In the present work, we performed a comprehensive study on the prot
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46

Lopera-Vasquez, R., M. Hamdi, V. Maillo, et al. "99 EXTRACELLULAR VESICLES OF BOVINE OVIDUCTAL FLUID MODIFY THE GENE EXPRESSION ON BOVINE IN VITRO-DERIVED EMBRYOS." Reproduction, Fertility and Development 28, no. 2 (2016): 179. http://dx.doi.org/10.1071/rdv28n2ab99.

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Extracellular vesicles (EVs) act as intercellular communicators through their protein, lipid, and mRNA content. The interaction of EVs from oviducal environment and the first stages of embryo development is currently an enigma. The aim of the present study was to evaluate the developmental competence and the expression profile of bovine blastocysts cultured with previously purified EVs recovered from ampullary and isthmic oviducal fluid (OF) under different centrifugal forces. OF-EVs recovered from oviducts of slaughtered heifers in early luteal phase were quantified with a nanoparticle tracki
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47

Muse, Oluwatoyosi, Rushad Patell, Christian Peters, et al. "The Unfolded Protein Response Causes Prothrombotic Transformation of Pancreatic Cancer Linking Tumor Progression with Cancer-Associated Thrombosis." Blood 134, Supplement_1 (2019): 632. http://dx.doi.org/10.1182/blood-2019-123544.

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Thrombosis is a common complication of advanced stage cancer. Yet the underlying mechanisms that link tumor progression to clot formation are poorly understood. The unfolded protein response (UPR) is associated with malignant transformation in pancreatic cancer, but whether or not activation of the UPR is linked to cancer thrombosis has not previously been evaluated. To determine whether UPR signaling functions in the prothrombotic transformation of pancreatic cancer, we exposed pancreatic adenocarcinoma cells (HPAF-II cells) to three UPR inducers (tunicamycin, triptolide or thapsigargin) that
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48

Ramachandran, Sowmya, Amit K. Verma, Kapil Dev, et al. "Role of Cytokines and Chemokines in NSCLC Immune Navigation and Proliferation." Oxidative Medicine and Cellular Longevity 2021 (July 16, 2021): 1–20. http://dx.doi.org/10.1155/2021/5563746.

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With over a million deaths every year around the world, lung cancer is found to be the most recurrent cancer among all types. Nonsmall cell lung carcinoma (NSCLC) amounts to about 85% of the entire cases. The other 15% owes it to small cell lung carcinoma (SCLC). Despite decades of research, the prognosis for NSCLC patients is poorly understood with treatment options limited. First, this article emphasises on the part that tumour microenvironment (TME) and its constituents play in lung cancer progression. This review also highlights the inflammatory (pro- or anti-) roles of different cytokines
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49

Cheerathodi, Mujeeb, Dingani Nkosi, Allaura S. Cone, Sara B. York, and David G. Meckes. "Epstein-Barr Virus LMP1 Modulates the CD63 Interactome." Viruses 13, no. 4 (2021): 675. http://dx.doi.org/10.3390/v13040675.

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Tetraspanin CD63 is a cluster of cell surface proteins with four transmembrane domains; it is associated with tetraspanin-enriched microdomains and typically localizes to late endosomes and lysosomes. CD63 plays an important role in the cellular trafficking of different proteins, EV cargo sorting, and vesicle formation. We have previously shown that CD63 is important in LMP1 trafficking to EVs, and this also affects LMP1-mediated intracellular signaling including MAPK/ERK, NF-κB, and mTOR activation. Using the BioID method combined with mass spectrometry, we sought to define the broad CD63 int
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50

Picca, Anna, Flora Guerra, Riccardo Calvani, et al. "Mitochondrial-Derived Vesicles as Candidate Biomarkers in Parkinson’s Disease: Rationale, Design and Methods of the EXosomes in PArkiNson Disease (EXPAND) Study." International Journal of Molecular Sciences 20, no. 10 (2019): 2373. http://dx.doi.org/10.3390/ijms20102373.

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The progressive loss of dopaminergic neurons in the nigro-striatal system is a major trait of Parkinson’s disease (PD), manifesting clinically as motor and non-motor symptoms. Mitochondrial dysfunction and oxidative stress are alleged pathogenic mechanisms underlying aggregation of misfolded α-synuclein that in turn triggers dopaminergic neurotoxicity. Peripheral processes, including inflammation, may precede and contribute to neurodegeneration. Whether mitochondrial dyshomeostasis in the central nervous system and systemic inflammation are linked to one another in PD is presently unclear. Ext
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