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      Extracellular Vesicles for the Diagnosis and Treatment of Parkinson’s Disease

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          Abstract

          Extracellular vesicles (EVs) shed by neurons and glia in the central nervous system carry a cargo of specific bioactive molecules, facilitating intercellular communication. However, in neurodegenerative disease conditions, EVs carry pathological miRNAs and/or proteins involved in spreading the disease. Such EVs are also found in the cerebrospinal fluid (CSF) or the circulating blood, the characterization of which could identify biomarkers linked to specific neurodegenerative diseases. Moreover, EVs secreted by various stem/progenitor cells carry therapeutic miRNAs and proteins, which have shown promise to alleviate symptoms and slow down the progression of neurodegenerative diseases. The ability of exogenously administered EVs to easily cross the blood-brain barrier with no risk for thrombosis and incorporate into neurons and glia has also opened up the possibility of using nano-sized EVs as carriers of therapeutic drugs or bioactive proteins. This review summarizes the role and function of EVs in alpha-synuclein-mediated neurodegeneration and the spread of alpha-synuclein from neurons to glia, leading to the activation of the inflammatory response in Parkinson’s disease (PD). Moreover, the promise of brain-derived EVs in the CSF and the circulating blood for biomarker discovery and the efficacy of stem/progenitor cell-derived EVs or EVs loaded with bioactive molecules such as dopamine, catalase, curcumin, and siRNAs, in alleviating Parkinsonian symptoms are discussed.

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          Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

          Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).
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            Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles.

            In the 1980s, exosomes were described as vesicles of endosomal origin secreted from reticulocytes. Interest increased around these extracellular vesicles, as they appeared to participate in several cellular processes. Exosomes bear proteins, lipids, and RNAs, mediating intercellular communication between different cell types in the body, and thus affecting normal and pathological conditions. Only recently, scientists acknowledged the difficulty of separating exosomes from other types of extracellular vesicles, which precludes a clear attribution of a particular function to the different types of secreted vesicles. To shed light into this complex but expanding field of science, this review focuses on the definition of exosomes and other secreted extracellular vesicles. Their biogenesis, their secretion, and their subsequent fate are discussed, as their functions rely on these important processes.
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              Staging of brain pathology related to sporadic Parkinson’s disease

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                Author and article information

                Journal
                Aging Dis
                Aging Dis
                Aging and Disease
                JKL International LLC
                2152-5250
                September 2021
                1 September 2021
                : 12
                : 6
                : 1438-1450
                Affiliations
                [1-ad-12-6-1438]Institute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University College of Medicine, College Station, Texas, USA
                Author notes
                [* ]Correspondence should be addressed to: Dr. Ashok K. Shetty, College of Medicine, Texas A&M University Health Science Center, College Station, TX 77845, USA. E-mail: akskrs@ 123456tamu.edu.
                Article
                ad-12-6-1438
                10.14336/AD.2021.0516
                8407884
                34527420
                985f78c6-7e1e-4d97-bc24-e9bd99fea169
                Copyright: © 2021 Upadhya et al.

                this is an open access article distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 26 February 2021
                : 15 May 2021
                : 16 May 2021
                Categories
                Review

                alpha-synuclein,dopamine,dopaminergic neurons,exosomes,extracellular vesicles,ev engineering,ev targeting,motor deficits,neuroinflammation,parkinson’s disease,substantia nigra

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