8
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Extracellular vesicles in the diagnosis and treatment of central nervous system diseases

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Extracellular vesicles, including exosomes and microvesicles, play a fundamental role in the activity of the nervous system, participating in signal transmission between neurons and providing the interaction of central nervous system with all body systems. In many neurodegenerative diseases, neurons pack toxic substances into vesicles and release them into the extracellular space, which leads to the spread of misfolded neurotoxic proteins. The contents of neuron-derived extracellular vesicles may indicate pathological changes in the central nervous system, and the analysis of extracellular vesicle molecular content contributes to the development of non-invasive methods for the diagnosis of many central nervous system diseases. Extracellular vesicles of neuronal origin can be isolated from various biological fluids due to their ability to cross the blood-brain barrier. Today, the diagnostic potential of almost all toxic proteins involved in nervous system disease pathogenesis, specifically α-synuclein, tau protein, superoxide dismutase 1, FUS, leucine-rich repeat kinase 2, as well as some synaptic proteins, has been well evidenced. Special attention is paid to extracellular RNAs mostly associated with extracellular vesicles, which are important in the onset and development of many neurodegenerative diseases. Depending on parental cell type, extracellular vesicles may have different therapeutic properties, including neuroprotective, regenerative, and anti-inflammatory. Due to nano size, biosafety, ability to cross the blood-brain barrier, possibility of targeted delivery and the lack of an immune response, extracellular vesicles are a promising vehicle for the delivery of therapeutic substances for the treatment of neurodegenerative diseases and drug delivery to the brain. This review describes modern approaches of diagnosis and treatment of central nervous system diseases using extracellular vesicles.

          Related collections

          Most cited references79

          • Record: found
          • Abstract: found
          • Article: not found

          Extracellular vesicle isolation and characterization: toward clinical application.

          Two broad categories of extracellular vesicles (EVs), exosomes and shed microvesicles (sMVs), which differ in size distribution as well as protein and RNA profiles, have been described. EVs are known to play key roles in cell-cell communication, acting proximally as well as systemically. This Review discusses the nature of EV subtypes, strategies for isolating EVs from both cell-culture media and body fluids, and procedures for quantifying EVs. We also discuss proteins selectively enriched in exosomes and sMVs that have the potential for use as markers to discriminate between EV subtypes, as well as various applications of EVs in clinical diagnosis.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Blood-brain barrier dysfunction and recovery after ischemic stroke.

            The blood-brain barrier (BBB) plays a vital role in regulating the trafficking of fluid, solutes and cells at the blood-brain interface and maintaining the homeostatic microenvironment of the CNS. Under pathological conditions, such as ischemic stroke, the BBB can be disrupted, followed by the extravasation of blood components into the brain and compromise of normal neuronal function. This article reviews recent advances in our knowledge of the mechanisms underlying BBB dysfunction and recovery after ischemic stroke. CNS cells in the neurovascular unit, as well as blood-borne peripheral cells constantly modulate the BBB and influence its breakdown and repair after ischemic stroke. The involvement of stroke risk factors and comorbid conditions further complicate the pathogenesis of neurovascular injury by predisposing the BBB to anatomical and functional changes that can exacerbate BBB dysfunction. Emphasis is also given to the process of long-term structural and functional restoration of the BBB after ischemic injury. With the development of novel research tools, future research on the BBB is likely to reveal promising potential therapeutic targets for protecting the BBB and improving patient outcome after ischemic stroke.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment

              Exosomes are cell-derived nanovesicles (50–150 nm), which mediate intercellular communication, and are candidate therapeutic agents. However, inefficiency of exosomal message transfer, such as mRNA, and lack of methods to create designer exosomes have hampered their development into therapeutic interventions. Here, we report a set of EXOsomal transfer into cells (EXOtic) devices that enable efficient, customizable production of designer exosomes in engineered mammalian cells. These genetically encoded devices in exosome producer cells enhance exosome production, specific mRNA packaging, and delivery of the mRNA into the cytosol of target cells, enabling efficient cell-to-cell communication without the need to concentrate exosomes. Further, engineered producer cells implanted in living mice could consistently deliver cargo mRNA to the brain. Therapeutic catalase mRNA delivery by designer exosomes attenuated neurotoxicity and neuroinflammation in in vitro and in vivo models of Parkinson’s disease, indicating the potential usefulness of the EXOtic devices for RNA delivery-based therapeutic applications.
                Bookmark

                Author and article information

                Journal
                Neural Regen Res
                Neural Regen Res
                NRR
                Neural Regeneration Research
                Wolters Kluwer - Medknow (India )
                1673-5374
                1876-7958
                April 2020
                18 October 2019
                : 15
                : 4
                : 586-596
                Affiliations
                [1 ]Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia
                [2 ]Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, The Russian Academy of Sciences, Moscow, Russia
                [3 ]School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire, UK
                Author notes
                [* ] Correspondence to: Albert A. Rizvanov, rizvanov@ 123456gmail.com .

                Author contributions: Manuscript design: VVS, AAR; manuscript writing and table design: AAS; data collection: VJ, DSC; figure production: KVK; manuscript and table revising: VVS, AAR. All authors contributed to, read and commented on the manuscript .

                Author information
                http://orcid.org/0000-0002-9427-5739
                Article
                NRR-15-586
                10.4103/1673-5374.266908
                6975137
                31638080
                eac5ec55-4891-4900-9f39-424e8f1064da
                Copyright: © Neural Regeneration Research

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 28 March 2019
                : 01 April 2019
                : 14 May 2019
                Categories
                Review

                biomarkers,cell-mediated therapy,central nervous system diseases,diagnosis,exosomes,extracellular rnas,extracellular vesicles,micrornas,microvesicles,neurodegenerative diseases

                Comments

                Comment on this article