Abstract
Extracellular vesicles (EVs) are a heterogeneous group of cell-derived membranous vesicles secreted by various cells in the extracellular space. Accumulating evidence shows that EVs regulate cell-to-cell communication and signaling in the pathological processes of various diseases by carrying proteins, lipids, and nucleic acids to recipient cells. Glia-derived EVs act as a double-edged sword in the pathogenesis of central nervous system (CNS) diseases. They may be vectors for the spread of diseases or act as effective clearance systems to protect tissues. In this review, we summarize recent studies on glia-derived EVs with a focus on their relationships with CNS diseases.
Funding source: the National Natural Science Foundation of China
Award Identifier / Grant number: 81630038, 81771634, 81701500, 81971433, 81971428
Funding source: National Key Project of Neonatal Children
Award Identifier / Grant number: 1311200003303
Acknowledgments
We would like to thank Editage [www.editage.cn] for English language editing.
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Research funding: This work was supported by the National Natural Science Foundation of China (81630038, 81771634, 81701500, 81971433, 81971428), and National Key Project of Neonatal Children (1311200003303).
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Conflict of interest statement: The authors declare that there is no conflict of interest.
References
Abels, E.R. and Breakefield, X.O. (2016). Introduction to extracellular vesicles: biogenesis, RNA cargo selection, content, release, and uptake. Cell. Mol. Neurobiol. 36: 301–312, https://doi.org/10.1007/s10571-016-0366-z.Search in Google Scholar PubMed PubMed Central
Allen, N.J. (2014). Astrocyte regulation of synaptic behavior. Annu. Rev. Cell Dev. Biol. 30: 439–463, https://doi.org/10.1146/annurev-cellbio-100913-013053.Search in Google Scholar PubMed
Allen, N.J. and Lyons, D.A. (2018). Glia as architects of central nervous system formation and function. Science 362: 181–185, https://doi.org/10.1126/science.aat0473.Search in Google Scholar PubMed PubMed Central
Anderson, M.A., Burda, J.E., Ren, Y., Ao, Y., O’Shea, T.M., Kawaguchi, R., Coppola, G., Khakh, B.S., Deming, T.J., and Sofroniew, M.V. (2016). Astrocyte scar formation aids central nervous system axon regeneration. Nature 532: 195–200, https://doi.org/10.1038/nature17623.Search in Google Scholar PubMed PubMed Central
Antonucci, F., Turola, E., Riganti, L., Caleo, M., Gabrielli, M., Perrotta, C., Novellino, L., Clementi, E., Giussani, P., Viani, P., et al.. (2012). Microvesicles released from microglia stimulate synaptic activity via enhanced sphingolipid metabolism. EMBO J. 31: 1231–1240, https://doi.org/10.1038/emboj.2011.489.Search in Google Scholar PubMed PubMed Central
Asai, H., Ikezu, S., Tsunoda, S., Medalla, M., Luebke, J., Haydar, T., Wolozin, B., Butovsky, O., Kugler, S., and Ikezu, T. (2015). Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat. Neurosci. 18: 1584–1593, https://doi.org/10.1038/nn.4132.Search in Google Scholar PubMed PubMed Central
Asikainen, S., Rudgalvyte, M., Heikkinen, L., Louhiranta, K., Lakso, M., Wong, G., and Nass, R. (2010). Global microRNA expression profiling of Caenorhabditis elegans Parkinson’s disease models. J. Mol. Neurosci. 41: 210–218, https://doi.org/10.1007/s12031-009-9325-1.Search in Google Scholar PubMed
Baker, S. and Gotz, J. (2016). A local insult of okadaic acid in wild-type mice induces tau phosphorylation and protein aggregation in anatomically distinct brain regions. Acta Neuropathol. Commun. 4: 32, https://doi.org/10.1186/s40478-016-0300-0.Search in Google Scholar PubMed PubMed Central
Basso, M. and Bonetto, V. (2016). Extracellular vesicles and a novel form of communication in the brain. Front. Neurosci. 10: 127, https://doi.org/10.3389/fnins.2016.00127.Search in Google Scholar PubMed PubMed Central
Basso, M., Pozzi, S., Tortarolo, M., Fiordaliso, F., Bisighini, C., Pasetto, L., Spaltro, G., Lidonnici, D., Gensano, F., Battaglia, E., et al.. (2013). Mutant copper-zinc superoxide dismutase (SOD1) induces protein secretion pathway alterations and exosome release in astrocytes: implications for disease spreading and motor neuron pathology in amyotrophic lateral sclerosis. J. Biol. Chem. 288: 15699–15711, https://doi.org/10.1074/jbc.m112.425066.Search in Google Scholar
Beneventano, M., Spampinato, S.F., Merlo, S., Chisari, M., Platania, P., Ragusa, M., Purrello, M., Nicoletti, F., and Sortino, M.A. (2017). Shedding of microvesicles from microglia contributes to the effects induced by metabotropic glutamate receptor 5 activation on neuronal death. Front. Pharmacol. 8: 812, https://doi.org/10.3389/fphar.2017.00812.Search in Google Scholar PubMed PubMed Central
Bianco, F., Pravettoni, E., Colombo, A., Schenk, U., Moller, T., Matteoli, M., and Verderio, C. (2005). Astrocyte-derived ATP induces vesicle shedding and IL-1 beta release from microglia. J. Immunol. 174: 7268–7277, https://doi.org/10.4049/jimmunol.174.11.7268.Search in Google Scholar PubMed
Blandford, S.N., Galloway, D.A., and Moore, C.S. (2018). The roles of extracellular vesicle microRNAs in the central nervous system. Glia 66: 2267–2278, https://doi.org/10.1002/glia.23445.Search in Google Scholar PubMed
Bliederhaeuser, C., Grozdanov, V., Speidel, A., Zondler, L., Ruf, W.P., Bayer, H., Kiechle, M., Feiler, M.S., Freischmidt, A., Brenner, D., et al.. (2016). Age-dependent defects of alpha-synuclein oligomer uptake in microglia and monocytes. Acta Neuropathol. 131: 379–391, https://doi.org/10.1007/s00401-015-1504-2.Search in Google Scholar PubMed
Brites, D. and Fernandes, A. (2015). Neuroinflammation and depression: microglia activation, extracellular microvesicles and microRNA dysregulation. Front. Cell. Neurosci. 9: 476, https://doi.org/10.3389/fncel.2015.00476.Search in Google Scholar PubMed PubMed Central
Budnik, V., Ruiz-Canada, C., and Wendler, F. (2016). Extracellular vesicles round off communication in the nervous system. Nat. Rev. Neurosci. 17: 160–172, https://doi.org/10.1038/nrn.2015.29.Search in Google Scholar PubMed PubMed Central
Casella, G., Colombo, F., Finardi, A., Descamps, H., Ill-Raga, G., Spinelli, A., Podini, P., Bastoni, M., Martino, G., Muzio, L., et al.. (2018). Extracellular vesicles containing IL-4 modulate neuroinflammation in a mouse model of multiple sclerosis. Mol. Ther. 26: 2107–2118, https://doi.org/10.1016/j.ymthe.2018.06.024.Search in Google Scholar PubMed PubMed Central
Chang, C., Lang, H., Geng, N., Wang, J., Li, N., and Wang, X. (2013). Exosomes of BV-2 cells induced by alpha-synuclein: important mediator of neurodegeneration in PD. Neurosci. Lett. 548: 190–195, https://doi.org/10.1016/j.neulet.2013.06.009.Search in Google Scholar PubMed
Chaudhuri, A.D., Dastgheyb, R.M., Yoo, S.W., Trout, A., Talbot, C.C.Jr., Hao, H., Witwer, K.W., and Haughey, N.J. (2018). TNFalpha and IL-1beta modify the miRNA cargo of astrocyte shed extracellular vesicles to regulate neurotrophic signaling in neurons. Cell Death Dis. 9: 363, https://doi.org/10.1038/s41419-018-0369-4.Search in Google Scholar PubMed PubMed Central
Chen, Y., Song, Y., Huang, J., Qu, M., Zhang, Y., Geng, J., Zhang, Z., Liu, J., and Yang, G.Y. (2017). Increased circulating exosomal miRNA-223 is associated with acute ischemic stroke. Front. Neurol. 8: 57, https://doi.org/10.3389/fneur.2017.00057.Search in Google Scholar PubMed PubMed Central
Chistiakov, D.A. and Chistiakov, A.A. (2017). alpha-Synuclein-carrying extracellular vesicles in Parkinson’s disease: deadly transmitters. Acta Neurol. Belg. 117: 43–51, https://doi.org/10.1007/s13760-016-0679-1.Search in Google Scholar PubMed
Chu, F., Shi, M., Zheng, C., Shen, D., Zhu, J., Zheng, X., and Cui, L. (2018). The roles of macrophages and microglia in multiple sclerosis and experimental autoimmune encephalomyelitis. J. Neuroimmunol. 318: 1–7, https://doi.org/10.1016/j.jneuroim.2018.02.015.Search in Google Scholar PubMed
Datta Chaudhuri, A., Dasgheyb, R.M., DeVine, L.R., Bi, H., Cole, R.N., and Haughey, N.J. (2020). Stimulus-dependent modifications in astrocyte-derived extracellular vesicle cargo regulate neuronal excitability. Glia 68: 128–144, https://doi.org/10.1002/glia.23708.Search in Google Scholar PubMed
Delpech, J.-C., Herron, S., Botros, M.B., and Ikezu, T. (2019). Neuroimmune crosstalk through extracellular vesicles in health and disease. Trends Neurosci. 42: 361–372, https://doi.org/10.1016/j.tins.2019.02.007.Search in Google Scholar PubMed PubMed Central
Dendrou, C.A., Fugger, L., and Friese, M.A. (2015). Immunopathology of multiple sclerosis. Nat. Rev. Immunol. 15: 545–558, https://doi.org/10.1038/nri3871.Search in Google Scholar PubMed
Dinkins, M.B., Dasgupta, S., Wang, G., Zhu, G., and Bieberich, E. (2014). Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer’s disease. Neurobiol. Aging 35: 1792–1800, https://doi.org/10.1016/j.neurobiolaging.2014.02.012.Search in Google Scholar PubMed PubMed Central
Diwanji, T.P., Engelman, A., Snider, J.W., and Mohindra, P. (2017). Epidemiology, diagnosis, and optimal management of glioma in adolescents and young adults. Adolesc. Health Med. Therapeut. 8: 99–113, https://doi.org/10.2147/ahmt.s53391.Search in Google Scholar PubMed PubMed Central
Drago, F., Lombardi, M., Prada, I., Gabrielli, M., Joshi, P., Cojoc, D., Franck, J., Fournier, I., Vizioli, J., and Verderio, C. (2017). ATP modifies the proteome of extracellular vesicles released by microglia and influences their action on astrocytes. Front. Pharmacol. 8, https://doi.org/10.3389/fphar.2017.00910.Search in Google Scholar PubMed PubMed Central
Dudvarski Stankovic, N., Teodorczyk, M., Ploen, R., Zipp, F., and Schmidt, M.H.H. (2015). Microglia–blood vessel interactions: a double-edged sword in brain pathologies. Acta Neuropathol. 131: 347–363, https://doi.org/10.1007/s00401-015-1524-y.Search in Google Scholar PubMed
Elbaz, B. and Popko, B. (2019). Molecular control of oligodendrocyte development. Trends Neurosci. 42: 263–277, https://doi.org/10.1016/j.tins.2019.01.002.Search in Google Scholar PubMed PubMed Central
Farooqi, A.A., Desai, N.N., Qureshi, M.Z., Librelotto, D.R.N., Gasparri, M.L., Bishayee, A., Nabavi, S.M., Curti, V., and Daglia, M. (2018). Exosome biogenesis, bioactivities and functions as new delivery systems of natural compounds. Biotechnol. Adv. 36: 328–334, https://doi.org/10.1016/j.biotechadv.2017.12.010.Search in Google Scholar PubMed
Feiler, M.S., Strobel, B., Freischmidt, A., Helferich, A.M., Kappel, J., Brewer, B.M., Li, D., Thal, D.R., Walther, P., Ludolph, A.C., et al.. (2015). TDP-43 is intercellularly transmitted across axon terminals. J. Cell Biol. 211: 897–911, https://doi.org/10.1083/jcb.201504057.Search in Google Scholar PubMed PubMed Central
Fernandes, H.J., Hartfield, E.M., Christian, H.C., Emmanoulidou, E., Zheng, Y., Booth, H., Bogetofte, H., Lang, C., Ryan, B.J., Sardi, S.P., et al.. (2016). ER stress and autophagic perturbations lead to elevated extracellular alpha-synuclein in GBA-N370S Parkinson’s iPSC-derived dopamine neurons. Stem Cell Rep. 6: 342–356, https://doi.org/10.1016/j.stemcr.2016.01.013.Search in Google Scholar PubMed PubMed Central
Fields, R.D., Woo, D.H., and Basser, P.J. (2015). Glial regulation of the neuronal connectome through local and long-distant communication. Neuron 86: 374–386, https://doi.org/10.1016/j.neuron.2015.01.014.Search in Google Scholar PubMed PubMed Central
Franz, C., Boing, A.N., Montag, M., Strowitzki, T., Markert, U.R., Mastenbroek, S., Nieuwland, R., and Toth, B. (2016). Extracellular vesicles in human follicular fluid do not promote coagulation. Reprod. Biomed. Online 33: 652–655, https://doi.org/10.1016/j.rbmo.2016.08.005.Search in Google Scholar PubMed
Frohlich, D., Kuo, W.P., Fruhbeis, C., Sun, J.J., Zehendner, C.M., Luhmann, H.J., Pinto, S., Toedling, J., Trotter, J., and Kramer-Albers, E.M. (2014). Multifaceted effects of oligodendroglial exosomes on neurons: impact on neuronal firing rate, signal transduction and gene regulation. Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 369, https://doi.org/10.1098/rstb.2013.0510.Search in Google Scholar PubMed PubMed Central
Fruhbeis, C., Frohlich, D., and Kramer-Albers, E.M. (2012). Emerging roles of exosomes in neuron-glia communication. Front. Physiol. 3: 119, https://doi.org/10.3389/fphys.2012.00119.Search in Google Scholar PubMed PubMed Central
Fruhbeis, C., Frohlich, D., Kuo, W.P., Amphornrat, J., Thilemann, S., Saab, A.S., Kirchhoff, F., Mobius, W., Goebbels, S., Nave, K.A., et al.. (2013). Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication. PLoS Biol. 11: e1001604, https://doi.org/10.1371/journal.pbio.1001604.Search in Google Scholar PubMed PubMed Central
Fruhbeis, C., Kuo-Elsner, W.P., Muller, C., Barth, K., Peris, L., Tenzer, S., Mobius, W., Werner, H.B., Nave, K.A., Frohlich, D., et al.. (2020). Oligodendrocytes support axonal transport and maintenance via exosome secretion. PLoS Biol. 18: e3000621, https://doi.org/10.1371/journal.pbio.3000621.Search in Google Scholar PubMed PubMed Central
Gabrielli, M., Battista, N., Riganti, L., Prada, I., Antonucci, F., Cantone, L., Matteoli, M., Maccarrone, M., and Verderio, C. (2015). Active endocannabinoids are secreted on extracellular membrane vesicles. EMBO Rep. 16: 213–220, https://doi.org/10.15252/embr.201439668.Search in Google Scholar PubMed PubMed Central
Galazka, G., Mycko, M.P., Selmaj, I., Raine, C.S., and Selmaj, K.W. (2018). Multiple sclerosis: serum-derived exosomes express myelin proteins. Mult. Scler. 24: 449–458, https://doi.org/10.1177/1352458517696597.Search in Google Scholar PubMed
Gayen, M., Bhomia, M., Balakathiresan, N., and Knollmann-Ritschel, B. (2020). Exosomal MicroRNAs released by activated astrocytes as potential neuroinflammatory biomarkers. Int. J. Mol. Sci. 21: 2312, https://doi.org/10.3390/ijms21072312.Search in Google Scholar PubMed PubMed Central
Goetzl, E.J., Mustapic, M., Kapogiannis, D., Eitan, E., Lobach, I.V., Goetzl, L., Schwartz, J.B., and Miller, B.L. (2016). Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer’s disease. Faseb. J. 30: 3853–3859, https://doi.org/10.1096/fj.201600756r.Search in Google Scholar
Goetzl, E.J., Schwartz, J.B., Abner, E.L., Jicha, G.A., and Kapogiannis, D. (2018). High complement levels in astrocyte-derived exosomes of Alzheimer disease. Ann. Neurol. 83: 544–552, https://doi.org/10.1002/ana.25172.Search in Google Scholar PubMed PubMed Central
Gomes, A.R., Sangani, N.B., Fernandes, T.G., Diogo, M.M., Curfs, L.M.G., and Reutelingsperger, C.P. (2020). Extracellular vesicles in CNS developmental disorders. Int. J. Mol. Sci. 21, https://doi.org/10.3390/ijms21249428.Search in Google Scholar PubMed PubMed Central
Gong, J., Korner, R., Gaitanos, L., and Klein, R. (2016). Exosomes mediate cell contact-independent ephrin-Eph signaling during axon guidance. J. Cell Biol. 214: 35–44, https://doi.org/10.1083/jcb.201601085.Search in Google Scholar PubMed PubMed Central
Gourlay, J., Morokoff, A.P., Luwor, R.B., Zhu, H.J., Kaye, A.H., and Stylli, S.S. (2017). The emergent role of exosomes in glioma. J. Clin. Neurosci. 35: 13–23, https://doi.org/10.1016/j.jocn.2016.09.021.Search in Google Scholar PubMed
Grey, M., Dunning, C.J., Gaspar, R., Grey, C., Brundin, P., Sparr, E., and Linse, S. (2015). Acceleration of alpha-synuclein aggregation by exosomes. J. Biol. Chem. 290: 2969–2982, https://doi.org/10.1074/jbc.m114.585703.Search in Google Scholar PubMed PubMed Central
Grimaldi, A., Serpe, C., Chece, G., Nigro, V., Sarra, A., Ruzicka, B., Relucenti, M., Familiari, G., Ruocco, G., Pascucci, G.R., et al.. (2019). Microglia-derived microvesicles affect microglia phenotype in glioma. Front. Cell. Neurosci. 13: 41, https://doi.org/10.3389/fncel.2019.00041.Search in Google Scholar PubMed PubMed Central
Guitart, K., Loers, G., Buck, F., Bork, U., Schachner, M., and Kleene, R. (2016). Improvement of neuronal cell survival by astrocyte-derived exosomes under hypoxic and ischemic conditions depends on prion protein. Glia 64: 896–910, https://doi.org/10.1002/glia.22963.Search in Google Scholar PubMed
Guo, M., Wang, J., Zhao, Y., Feng, Y., Han, S., Dong, Q., Cui, M., and Tieu, K. (2020). Microglial exosomes facilitate alpha-synuclein transmission in Parkinson’s disease. Brain 143: 1476–1497, https://doi.org/10.1093/brain/awaa090.Search in Google Scholar PubMed PubMed Central
Hill, A.F. (2019). Extracellular vesicles and neurodegenerative diseases. J. Neurosci. 39: 9269–9273, https://doi.org/10.1523/jneurosci.0147-18.2019.Search in Google Scholar PubMed PubMed Central
Hira, K., Ueno, Y., Tanaka, R., Miyamoto, N., Yamashiro, K., Inaba, T., Urabe, T., Okano, H., and Hattori, N. (2018). Astrocyte-derived exosomes treated with a semaphorin 3A inhibitor enhance stroke recovery via prostaglandin D2 synthase. Stroke 49: 2483–2494, https://doi.org/10.1161/strokeaha.118.021272.Search in Google Scholar
Ho, A.K., Horton, M.C., Landwehrmeyer, G.B., Burgunder, J.M., Tennant, A., and European Huntington’s Disease, N. (2019). Meaningful and measurable health domains in huntington’s disease: large-scale validation of the huntington’s disease health-related quality of life questionnaire across severity stages. Value Health 22: 712–720, https://doi.org/10.1016/j.jval.2019.01.016.Search in Google Scholar PubMed
Holm, M.M., Kaiser, J., and Schwab, M.E. (2018). Extracellular vesicles: multimodal envoys in neural maintenance and repair. Trends Neurosci. 41: 360–372, https://doi.org/10.1016/j.tins.2018.03.006.Search in Google Scholar PubMed
Hombach-Klonisch, S., Mehrpour, M., Shojaei, S., Harlos, C., Pitz, M., Hamai, A., Siemianowicz, K., Likus, W., Wiechec, E., Toyota, B.D., et al.. (2018). Glioblastoma and chemoresistance to alkylating agents: involvement of apoptosis, autophagy, and unfolded protein response. Pharmacol. Therapeut. 184: 13–41, https://doi.org/10.1016/j.pharmthera.2017.10.017.Search in Google Scholar PubMed
Hong, S., Beja-Glasser, V.F., Nfonoyim, B.M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K.M., Shi, Q., Rosenthal, A., Barres, B.A., et al.. (2016). Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 352: 712–716, https://doi.org/10.1126/science.aad8373.Search in Google Scholar PubMed PubMed Central
Hong, Y., Zhao, T., Li, X.J., and Li, S. (2017). Mutant huntingtin inhibits alphaB-crystallin expression and impairs exosome secretion from astrocytes. J. Neurosci. 37: 9550–9563, https://doi.org/10.1523/jneurosci.1418-17.2017.Search in Google Scholar PubMed PubMed Central
Huang, S., Ge, X., Yu, J., Han, Z., Yin, Z., Li, Y., Chen, F., Wang, H., Zhang, J., and Lei, P. (2018). Increased miR-124-3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowth via their transfer into neurons. Faseb. J. 32: 512–528, https://doi.org/10.1096/fj.201700673r.Search in Google Scholar PubMed
Hurley, J.H. (2008). ESCRT complexes and the biogenesis of multivesicular bodies. Curr. Opin. Cell Biol. 20: 4–11, https://doi.org/10.1016/j.ceb.2007.12.002.Search in Google Scholar PubMed PubMed Central
Jakel, S. and Dimou, L. (2017). Glial cells and their function in the adult brain: a journey through the history of their ablation. Front. Cell. Neurosci. 11: 24, https://doi.org/10.3389/fncel.2017.00024.Search in Google Scholar PubMed PubMed Central
Janowska, J., Gargas, J., Ziemka-Nalecz, M., Zalewska, T., Buzanska, L., and Sypecka, J. (2019). Directed glial differentiation and transdifferentiation for neural tissue regeneration. Exp. Neurol. 319: 112813, https://doi.org/10.1016/j.expneurol.2018.08.010.Search in Google Scholar PubMed
Jeon, I., Cicchetti, F., Cisbani, G., Lee, S., Li, E., Bae, J., Lee, N., Li, L., Im, W., Kim, M., et al.. (2016). Human-to-mouse prion-like propagation of mutant huntingtin protein. Acta Neuropathol. 132: 577–592, https://doi.org/10.1007/s00401-016-1582-9.Search in Google Scholar PubMed PubMed Central
Jha, M.K., Kim, J.H., Song, G.J., Lee, W.H., Lee, I.K., Lee, H.W., An, S.S.A., Kim, S., and Suk, K. (2018). Functional dissection of astrocyte-secreted proteins: implications in brain health and diseases. Prog. Neurobiol. 162: 37–69, https://doi.org/10.1016/j.pneurobio.2017.12.003.Search in Google Scholar PubMed
Joshi, P., Turola, E., Ruiz, A., Bergami, A., Libera, D.D., Benussi, L., Giussani, P., Magnani, G., Comi, G., Legname, G., et al.. (2014). Microglia convert aggregated amyloid-beta into neurotoxic forms through the shedding of microvesicles. Cell Death Differ. 21: 582–593, https://doi.org/10.1038/cdd.2013.180.Search in Google Scholar PubMed PubMed Central
Kalra, H., Drummen, G.P., and Mathivanan, S. (2016). Focus on extracellular vesicles: introducing the next small big thing. Int. J. Mol. Sci. 17: 170, https://doi.org/10.3390/ijms17020170.Search in Google Scholar PubMed PubMed Central
Kam, T.I., Mao, X., Park, H., Chou, S.C., Karuppagounder, S.S., Umanah, G.E., Yun, S.P., Brahmachari, S., Panicker, N., Chen, R., et al.. (2018). Poly(ADP-ribose) drives pathologic alpha-synuclein neurodegeneration in Parkinson’s disease. Science 362, https://doi.org/10.1126/science.aat8407.Search in Google Scholar PubMed PubMed Central
Kao, C.Y. and Papoutsakis, E.T. (2019). Extracellular vesicles: exosomes, microparticles, their parts, and their targets to enable their biomanufacturing and clinical applications. Curr. Opin. Biotechnol. 60: 89–98, https://doi.org/10.1016/j.copbio.2019.01.005.Search in Google Scholar PubMed
Kawachi, I. and Lassmann, H. (2017). Neurodegeneration in multiple sclerosis and neuromyelitis optica. J. Neurol. Neurosurg. Psychiatr. 88: 137–145, https://doi.org/10.1136/jnnp-2016-313300.Search in Google Scholar PubMed
Khakh, B.S. and McCarthy, K.D. (2015). Astrocyte calcium signaling: from observations to functions and the challenges therein. Cold Spring Harb. Perspect Biol. 7: a020404, https://doi.org/10.1101/cshperspect.a020404.Search in Google Scholar PubMed PubMed Central
Kramer-Albers, E.M., Bretz, N., Tenzer, S., Winterstein, C., Mobius, W., Berger, H., Nave, K.A., Schild, H., and Trotter, J. (2007). Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: trophic support for axons? Proteonomics Clin. Appl. 1: 1446–1461, https://doi.org/10.1002/prca.200700522.Search in Google Scholar PubMed
Kumar, A., Stoica, B.A., Loane, D.J., Yang, M., Abulwerdi, G., Khan, N., Kumar, A., Thom, S.R., and Faden, A.I. (2017). Microglial-derived microparticles mediate neuroinflammation after traumatic brain injury. J. Neuroinflammation 14, https://doi.org/10.1186/s12974-017-0819-4.Search in Google Scholar PubMed PubMed Central
L’Episcopo, F., Tirolo, C., Serapide, M.F., Caniglia, S., Testa, N., Leggio, L., Vivarelli, S., Iraci, N., Pluchino, S., and Marchetti, B. (2018). Microglia polarization, gene-environment interactions and wnt/beta-catenin signaling: emerging roles of glia-neuron and glia-stem/neuroprogenitor crosstalk for dopaminergic neurorestoration in aged parkinsonian brain. Front. Aging Neurosci. 10: 12, https://doi.org/10.3389/fnagi.2018.00012.Search in Google Scholar PubMed PubMed Central
Lafourcade, C., Ramirez, J.P., Luarte, A., Fernandez, A., and Wyneken, U. (2016). MiRNAs in astrocyte-derived exosomes as possible mediators of neuronal plasticity. J. Exp. Neurosci. 10: 1–9, https://doi.org/10.4137/JEN.S39916.Search in Google Scholar PubMed PubMed Central
Larson, V.A., Mironova, Y., Vanderpool, K.G., Waisman, A., Rash, J.E., Agarwal, A., and Bergles, D.E. (2018). Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility. Elife 7, https://doi.org/10.7554/elife.34829.Search in Google Scholar
Lee, S., Mankhong, S., and Kang, J.H. (2019). Extracellular vesicle as a source of alzheimer’s biomarkers: opportunities and challenges. Int. J. Mol. Sci. 20, https://doi.org/10.3390/ijms20071728.Search in Google Scholar PubMed PubMed Central
Lee, S.T., Im, W., Ban, J.J., Lee, M., Jung, K.H., Lee, S.K., Chu, K., and Kim, M. (2017). Exosome-based delivery of miR-124 in a huntington’s disease model. J. Mov. Disord. 10: 45–52, https://doi.org/10.14802/jmd.16054.Search in Google Scholar PubMed PubMed Central
Li, D., Huang, S., Yin, Z., Zhu, J., Ge, X., Han, Z., Tan, J., Zhang, S., Zhao, J., Chen, F., et al.. (2019a). Increases in miR-124-3p in microglial exosomes confer neuroprotective effects by targeting FIP200-mediated neuronal autophagy following traumatic brain injury. Neurochem. Res. 44: 1903–1923, https://doi.org/10.1007/s11064-019-02825-1.Search in Google Scholar PubMed
Li, F., Xie, X.Y., Sui, X.F., Wang, P., Chen, Z., and Zhang, J.B. (2020). Profile of pathogenic proteins and MicroRNAs in plasma-derived extracellular vesicles in alzheimer’s disease: a pilot study. Neuroscience 432: 240–246, https://doi.org/10.1016/j.neuroscience.2020.02.044.Search in Google Scholar PubMed
Li, H., Luo, Y., Zhu, L., Hua, W., Zhang, Y., Zhang, H., Zhang, L., Li, Z., Xing, P., Zhang, Y., et al.. (2019b). Glia-derived exosomes: promising therapeutic targets. Life Sci. 239: 116951, https://doi.org/10.1016/j.lfs.2019.116951.Search in Google Scholar PubMed
Li, J., Zhang, S., Liu, X., Han, D., Xu, J., and Ma, Y. (2018). Neuroprotective effects of leonurine against oxygen-glucose deprivation by targeting Cx36/CaMKII in PC12 cells. PloS One 13: e0200705, https://doi.org/10.1371/journal.pone.0200705.Search in Google Scholar PubMed PubMed Central
Li, N., Wu, Y., Zhu, L., Huang, Y., Liu, Z., Shi, M., Soltys, D., Zhang, J., and Chang, Q. (2019c). Extracellular microvesicles-derived from microglia treated with unaggregated alpha-synuclein attenuate mitochondrial fission and toxicity-induced by Parkinsonian toxin MPP. Biochem. Biophys. Res. Commun. 517: 642–647, https://doi.org/10.1016/j.bbrc.2019.07.084.Search in Google Scholar PubMed
Liu, L.R., Liu, J.C., Bao, J.S., Bai, Q.Q., and Wang, G.Q. (2020). Interaction of microglia and astrocytes in the neurovascular unit. Front. Immunol. 11: 1024, https://doi.org/10.3389/fimmu.2020.01024.Search in Google Scholar PubMed PubMed Central
Lo Cicero, A., Stahl, P.D., and Raposo, G. (2015). Extracellular vesicles shuffling intercellular messages: for good or for bad. Curr. Opin. Cell Biol. 35: 69–77, https://doi.org/10.1016/j.ceb.2015.04.013.Search in Google Scholar PubMed
Long, X., Yao, X., Jiang, Q., Yang, Y., He, X., Tian, W., Zhao, K., and Zhang, H. (2020). Astrocyte-derived exosomes enriched with miR-873a-5p inhibit neuroinflammation via microglia phenotype modulation after traumatic brain injury. J. Neuroinflammation 17: 89, https://doi.org/10.1186/s12974-020-01761-0.Search in Google Scholar PubMed PubMed Central
Loov, C., Scherzer, C.R., Hyman, B.T., Breakefield, X.O., and Ingelsson, M. (2016). Alpha-synuclein in extracellular vesicles: functional implications and diagnostic opportunities. Cell. Mol. Neurobiol. 36: 437–448, https://doi.org/10.1007/s10571-015-0317-0.Search in Google Scholar PubMed
Louis, D.N., Perry, A., Reifenberger, G., von Deimling, A., Figarella-Branger, D., Cavenee, W.K., Ohgaki, H., Wiestler, O.D., Kleihues, P., and Ellison, D.W. (2016). The 2016 world health organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 131: 803–820, https://doi.org/10.1007/s00401-016-1545-1.Search in Google Scholar PubMed
Luarte, A., Cisternas, P., Caviedes, A., Batiz, L.F., Lafourcade, C., Wyneken, U., and Henzi, R. (2017). Astrocytes at the hub of the stress response: potential modulation of neurogenesis by miRNAs in astrocyte-derived exosomes. Stem Cell. Int. 2017: 1719050, https://doi.org/10.1155/2017/1719050.Search in Google Scholar PubMed PubMed Central
Ma, C., Chen, H., Zhang, S., Yan, Y., Wu, R., Wang, Y., Liu, Y., Yang, L., and Liu, M. (2019). Exosomal and extracellular HMGB1 have opposite effects on SASH1 expression in rat astrocytes and glioma C6 cells. Biochem. Biophys. Res. Commun. 518: 325–330, https://doi.org/10.1016/j.bbrc.2019.08.057.Search in Google Scholar PubMed
Mao, S., Sun, Q., Xiao, H., Zhang, C., and Li, L. (2015). Secreted miR-34a in astrocytic shedding vesicles enhanced the vulnerability of dopaminergic neurons to neurotoxins by targeting Bcl-2. Protein Cell 6: 529–540, https://doi.org/10.1007/s13238-015-0168-y.Search in Google Scholar PubMed PubMed Central
Marc A Antonyak, K.F.W. and Cerione, R.A. (2012). R(h)oads to microvesicles. Small GTPases 3: 219–224, https://doi.org/10.4161/sgtp.20755.Search in Google Scholar PubMed PubMed Central
Marchetti, B., Leggio, L., L’Episcopo, F., Vivarelli, S., Tirolo, C., Paterno, G., Giachino, C., Caniglia, S., Serapide, M.F., and Iraci, N. (2020). Glia-derived extracellular vesicles in Parkinson’s disease. J. Clin. Med. 9, https://doi.org/10.3390/jcm9061941.Search in Google Scholar PubMed PubMed Central
Masgrau, R., Guaza, C., Ransohoff, R.M., and Galea, E. (2017). Should we stop saying ’glia’ and ’neuroinflammation’? Trends Mol. Med. 23: 486–500, https://doi.org/10.1016/j.molmed.2017.04.005.Search in Google Scholar PubMed
Massenzio, F., Pena-Altamira, E., Petralla, S., Virgili, M., Zuccheri, G., Miti, A., Polazzi, E., Mengoni, I., Piffaretti, D., and Monti, B. (2018). Microglial overexpression of fALS-linked mutant SOD1 induces SOD1 processing impairment, activation and neurotoxicity and is counteracted by the autophagy inducer trehalose. Biochim. Biophys. Acta (BBA) - Mol. Basis Dis. 1864: 3771–3785, https://doi.org/10.1016/j.bbadis.2018.10.013.Search in Google Scholar PubMed
McKee, C.A. and Lukens, J.R. (2016). Emerging roles for the immune system in traumatic brain injury. Front. Immunol. 7: 556, https://doi.org/10.3389/fimmu.2016.00556.Search in Google Scholar PubMed PubMed Central
Minciacchi, V.R., Freeman, M.R., and Di Vizio, D. (2015). Extracellular vesicles in cancer: exosomes, microvesicles and the emerging role of large oncosomes. Semin. Cell Dev. Biol. 40: 41–51, https://doi.org/10.1016/j.semcdb.2015.02.010.Search in Google Scholar PubMed PubMed Central
Mrowczynski, O.D., Zacharia, B.E., and Connor, J.R. (2019). Exosomes and their implications in central nervous system tumor biology. Prog. Neurobiol. 172: 71–83, https://doi.org/10.1016/j.pneurobio.2018.06.006.Search in Google Scholar PubMed
Muller, L., Muller-Haegele, S., Mitsuhashi, M., Gooding, W., Okada, H., and Whiteside, T.L. (2015). Exosomes isolated from plasma of glioma patients enrolled in a vaccination trial reflect antitumor immune activity and might predict survival. OncoImmunology 4: e1008347, https://doi.org/10.1080/2162402x.2015.1008347.Search in Google Scholar PubMed PubMed Central
Muralidharan-Chari, V., Clancy, J., Plou, C., Romao, M., Chavrier, P., Raposo, G., and D’Souza-Schorey, C. (2009). ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr. Biol. 19: 1875–1885, https://doi.org/10.1016/j.cub.2009.09.059.Search in Google Scholar PubMed PubMed Central
Muraoka, S., DeLeo, A.M., Sethi, M.K., Yukawa-Takamatsu, K., Yang, Z., Ko, J., Hogan, J.D., Ruan, Z., You, Y., Wang, Y., et al.. (2020). Proteomic and biological profiling of extracellular vesicles from Alzheimer’s disease human brain tissues. Alzheimer’s Dementia 16: 896–907, https://doi.org/10.1002/alz.12089.Search in Google Scholar PubMed PubMed Central
Murgoci, A.N., Cizkova, D., Majerova, P., Petrovova, E., Medvecky, L., Fournier, I., and Salzet, M. (2018). Brain-cortex microglia-derived exosomes: nanoparticles for glioma therapy. ChemPhysChem : Eur. J. Chem. Phys. Phys. Chem. 19: 1205–1214, https://doi.org/10.1002/cphc.201701198.Search in Google Scholar PubMed
Nave, K.A. and Trapp, B.D. (2008). Axon-glial signaling and the glial support of axon function. Annu. Rev. Neurosci. 31: 535–561, https://doi.org/10.1146/annurev.neuro.30.051606.094309.Search in Google Scholar PubMed
Neal, M. and Richardson, J.R. (2018). Epigenetic regulation of astrocyte function in neuroinflammation and neurodegeneration. Biochim. Biophys. Acta (BBA) - Mol. Basis Dis. 1864: 432–443, https://doi.org/10.1016/j.bbadis.2017.11.004.Search in Google Scholar PubMed PubMed Central
Nigro, A., Colombo, F., Casella, G., Finardi, A., Verderio, C., and Furlan, R. (2016). Myeloid extracellular vesicles: messengers from the demented brain. Front. Immunol. 7: 17, https://doi.org/10.3389/fimmu.2016.00017.Search in Google Scholar PubMed PubMed Central
Niu, X., Chen, J., and Gao, J. (2019). Nanocarriers as a powerful vehicle to overcome blood-brain barrier in treating neurodegenerative diseases: focus on recent advances. Asian J. Pharm. Sci. 14: 480–496, https://doi.org/10.1016/j.ajps.2018.09.005.Search in Google Scholar PubMed PubMed Central
Nogueras-Ortiz, C.J., Mahairaki, V., Delgado-Peraza, F., Das, D., Avgerinos, K., Eren, E., Hentschel, M., Goetzl, E.J., Mattson, M.P., and Kapogiannis, D. (2020). Astrocyte- and neuron-derived extracellular vesicles from alzheimer’s disease patients effect complement-mediated neurotoxicity. Cells 9, https://doi.org/10.3390/cells9071618.Search in Google Scholar PubMed PubMed Central
Okolie, O., Bago, J.R., Schmid, R.S., Irvin, D.M., Bash, R.E., Miller, C.R., and Hingtgen, S.D. (2016). Reactive astrocytes potentiate tumor aggressiveness in a murine glioma resection and recurrence model. Neuro Oncol. 18: 1622–1633, https://doi.org/10.1093/neuonc/now117.Search in Google Scholar PubMed PubMed Central
Olanrewaju, A.A., and Hakami, R.M. (2020). The messenger apps of the cell: extracellular vesicles as regulatory messengers of microglial function in the CNS. J. Neuroimmune Pharmacol 15: 473–486, https://doi.org/10.1007/s11481-020-09916-9.Search in Google Scholar PubMed PubMed Central
Osier, N., Motamedi, V., Edwards, K., Puccio, A., Diaz-Arrastia, R., Kenney, K., and Gill, J. (2018). Exosomes in acquired neurological disorders: new insights into pathophysiology and treatment. Mol. Neurobiol. 55: 9280–9293, https://doi.org/10.1007/s12035-018-1054-4.Search in Google Scholar PubMed
Panaro, M.A., Benameur, T., and Porro, C. (2020a). Extracellular vesicles miRNA cargo for microglia polarization in traumatic brain injury. Biomolecules 10, https://doi.org/10.3390/biom10060901.Search in Google Scholar PubMed PubMed Central
Panaro, M.A., Corrado, A., Benameur, T., Paolo, C.F., Cici, D., and Porro, C. (2020b). The emerging role of curcumin in the modulation of TLR-4 signaling pathway: focus on neuroprotective and anti-rheumatic properties. Int. J. Mol. Sci. 21, https://doi.org/10.3390/ijms21072299.Search in Google Scholar PubMed PubMed Central
Paolicelli, R.C., Bergamini, G., and Rajendran, L. (2019). Cell-to-cell communication by extracellular vesicles: focus on microglia. Neuroscience 405: 148–157, https://doi.org/10.1016/j.neuroscience.2018.04.003.Search in Google Scholar PubMed
Pardeshi, R., Bolshette, N., Gadhave, K., Ahire, A., Ahmed, S., Cassano, T., Gupta, V.B., and Lahkar, M. (2017). Insulin signaling: an opportunistic target to minify the risk of Alzheimer’s disease. Psychoneuroendocrinology 83: 159–171, https://doi.org/10.1016/j.psyneuen.2017.05.004.Search in Google Scholar PubMed
Park, S.Y., Choi, Y.W., and Park, G. (2018). Nrf2-mediated neuroprotection against oxygen-glucose deprivation/reperfusion injury by emodin via AMPK-dependent inhibition of GSK-3beta. J. Pharm. Pharmacol. 70: 525–535, https://doi.org/10.1111/jphp.12885.Search in Google Scholar PubMed
Pascua-Maestro, R., Gonzalez, E., Lillo, C., Ganfornina, M.D., Falcon-Perez, J.M., and Sanchez, D. (2018). Extracellular vesicles secreted by astroglial cells transport apolipoprotein D to neurons and mediate neuronal survival upon oxidative stress. Front. Cell. Neurosci. 12: 526, https://doi.org/10.3389/fncel.2018.00526.Search in Google Scholar PubMed PubMed Central
Patel, K. and Sun, D. (2016). Strategies targeting endogenous neurogenic cell response to improve recovery following traumatic brain injury. Brain Res. 1640: 104–113, https://doi.org/10.1016/j.brainres.2016.01.055.Search in Google Scholar PubMed PubMed Central
Pei, X., Li, Y., Zhu, L., and Zhou, Z. (2019). Astrocyte-derived exosomes suppress autophagy and ameliorate neuronal damage in experimental ischemic stroke. Exp. Cell Res. 382: 111474, https://doi.org/10.1016/j.yexcr.2019.06.019.Search in Google Scholar PubMed
Picca, A., Guerra, F., Calvani, R., Bucci, C., Lo Monaco, M.R., Bentivoglio, A.R., Landi, F., Bernabei, R., and Marzetti, E. (2019). Mitochondrial-derived vesicles as candidate biomarkers in Parkinson’s disease: rationale, design and methods of the EXosomes in Parkinson disease (EXPAND) study. Int. J. Mol. Sci. 20, https://doi.org/10.3390/ijms20102373.Search in Google Scholar PubMed PubMed Central
Pieragostino, D., Lanuti, P., Cicalini, I., Cufaro, M.C., Ciccocioppo, F., Ronci, M., Simeone, P., Onofrj, M., van der Pol, E., Fontana, A., et al.. (2019). Proteomics characterization of extracellular vesicles sorted by flow cytometry reveals a disease-specific molecular cross-talk from cerebrospinal fluid and tears in multiple sclerosis. J. Proteomics 204: 103403, https://doi.org/10.1016/j.jprot.2019.103403.Search in Google Scholar PubMed
Pistono, C., Bister, N., Stanova, I., and Malm, T. (2020). Glia-derived extracellular vesicles: role in central nervous system communication in health and disease. Front. Cell Dev. Biol. 8: 623771, https://doi.org/10.3389/fcell.2020.623771.Search in Google Scholar PubMed PubMed Central
Polanco, J.C., Li, C., Bodea, L.G., Martinez-Marmol, R., Meunier, F.A., and Gotz, J. (2018). Amyloid-beta and tau complexity - towards improved biomarkers and targeted therapies. Nat. Rev. Neurol. 14: 22–39, https://doi.org/10.1038/nrneurol.2017.162.Search in Google Scholar PubMed
Porro, C., Trotta, T., and Panaro, M.A. (2015). Microvesicles in the brain: biomarker, messenger or mediator? J. Neuroimmunol. 288: 70–78, https://doi.org/10.1016/j.jneuroim.2015.09.006.Search in Google Scholar PubMed
Prada, I., Gabrielli, M., Turola, E., Iorio, A., D’Arrigo, G., Parolisi, R., De Luca, M., Pacifici, M., Bastoni, M., Lombardi, M., et al.. (2018). Glia-to-neuron transfer of miRNAs via extracellular vesicles: a new mechanism underlying inflammation-induced synaptic alterations. Acta Neuropathol. 135: 529–550, https://doi.org/10.1007/s00401-017-1803-x.Search in Google Scholar PubMed PubMed Central
Quail, D.F. and Joyce, J.A. (2017). The microenvironmental landscape of brain tumors. Canc. Cell 31: 326–341, https://doi.org/10.1016/j.ccell.2017.02.009.Search in Google Scholar PubMed PubMed Central
Quezada, C., Torres, A., Niechi, I., Uribe, D., Contreras-Duarte, S., Toledo, F., San Martin, R., Gutierrez, J., and Sobrevia, L. (2018). Role of extracellular vesicles in glioma progression. Mol. Aspect. Med. 60: 38–51, https://doi.org/10.1016/j.mam.2017.12.003.Search in Google Scholar PubMed
Raposo, G. and Stoorvogel, W. (2013). Extracellular vesicles: exosomes, microvesicles, and friends. J. Cell Biol. 200: 373–383, https://doi.org/10.1083/jcb.201211138.Search in Google Scholar PubMed PubMed Central
Saenz-Cuesta, M., Osorio-Querejeta, I., and Otaegui, D. (2014). Extracellular vesicles in multiple sclerosis: what are they telling us? Front. Cell. Neurosci. 8: 100, https://doi.org/10.2217/bmm.14.9.Search in Google Scholar PubMed
Saint-Pol, J., Gosselet, F., Duban-Deweer, S., Pottiez, G., and Karamanos, Y. (2020). Targeting and crossing the blood-brain barrier with extracellular vesicles. Cells 9, https://doi.org/10.3390/cells9040851.Search in Google Scholar PubMed PubMed Central
Sami Saribas, A., Cicalese, S., Ahooyi, T.M., Khalili, K., Amini, S., and Sariyer, I.K. (2017). HIV-1 Nef is released in extracellular vesicles derived from astrocytes: evidence for Nef-mediated neurotoxicity. Cell Death Dis. 8: e2542, https://doi.org/10.1038/cddis.2016.467.Search in Google Scholar PubMed PubMed Central
Sanai, N. and Berger, M.S. (2018). Surgical oncology for gliomas: the state of the art. Nat. Rev. Clin. Oncol. 15: 112–125, https://doi.org/10.1038/nrclinonc.2017.171.Search in Google Scholar PubMed
Schlienger, S., Campbell, S., and Claing, A. (2014). ARF1 regulates the Rho/MLC pathway to control EGF-dependent breast cancer cell invasion. Mol. Biol. Cell 25: 17–29, https://doi.org/10.1091/mbc.e13-06-0335.Search in Google Scholar
Sedgwick, A.E., Clancy, J.W., Olivia Balmert, M., and D’Souza-Schorey, C. (2015). Extracellular microvesicles and invadopodia mediate non-overlapping modes of tumor cell invasion. Sci. Rep. 5: 14748, https://doi.org/10.1038/srep14748.Search in Google Scholar PubMed PubMed Central
Silverman, J.M., Fernando, S.M., Grad, L.I., Hill, A.F., Turner, B.J., Yerbury, J.J., and Cashman, N.R. (2016). Disease mechanisms in ALS: misfolded SOD1 transferred through exosome-dependent and exosome-independent pathways. Cell. Mol. Neurobiol. 36: 377–381, https://doi.org/10.1007/s10571-015-0294-3.Search in Google Scholar PubMed
Sin, W.C., Aftab, Q., Bechberger, J.F., Leung, J.H., Chen, H., and Naus, C.C. (2016). Astrocytes promote glioma invasion via the gap junction protein connexin43. Oncogene 35: 1504–1516, https://doi.org/10.1038/onc.2015.210.Search in Google Scholar PubMed
Sofroniew, M.V. (2014). Astrogliosis. Cold Spring Harb. Perspect. Biol. 7: a020420, https://doi.org/10.1101/cshperspect.a020420.Search in Google Scholar PubMed PubMed Central
Sollvander, S., Nikitidou, E., Brolin, R., Soderberg, L., Sehlin, D., Lannfelt, L., and Erlandsson, A. (2016). Accumulation of amyloid-beta by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons. Mol. Neurodegener. 11: 38, https://doi.org/10.1186/s13024-016-0098-z.Search in Google Scholar PubMed PubMed Central
Soria, F.N., Pampliega, O., Bourdenx, M., Meissner, W.G., Bezard, E., and Dehay, B. (2017). Exosomes, an unmasked culprit in neurodegenerative diseases. Front. Neurosci. 11: 26, https://doi.org/10.3389/fnins.2017.00026.Search in Google Scholar PubMed PubMed Central
Sproviero, D., La Salvia, S., Giannini, M., Crippa, V., Gagliardi, S., Bernuzzi, S., Diamanti, L., Ceroni, M., Pansarasa, O., Poletti, A., et al.. (2018). Pathological proteins are transported by extracellular vesicles of sporadic amyotrophic lateral sclerosis patients. Front. Neurosci. 12: 487, https://doi.org/10.3389/fnins.2018.00487.Search in Google Scholar PubMed PubMed Central
Stuendl, A., Kunadt, M., Kruse, N., Bartels, C., Moebius, W., Danzer, K.M., Mollenhauer, B., and Schneider, A. (2016). Induction of alpha-synuclein aggregate formation by CSF exosomes from patients with Parkinson’s disease and dementia with Lewy bodies. Brain 139: 481–494, https://doi.org/10.1093/brain/awv346.Search in Google Scholar PubMed PubMed Central
Stuffers, S., Sem Wegner, C., Stenmark, H., and Brech, A. (2009). Multivesicular endosome biogenesis in the absence of ESCRTs. Traffic 10: 925–937, https://doi.org/10.1111/j.1600-0854.2009.00920.x.Search in Google Scholar PubMed
Sveinbjornsdottir, S. (2016). The clinical symptoms of Parkinson’s disease. J. Neurochem. 139: 318–324, https://doi.org/10.1111/jnc.13691.Search in Google Scholar PubMed
Szepesi, Z., Manouchehrian, O., Bachiller, S., and Deierborg, T. (2018). Bidirectional microglia-neuron communication in health and disease. Front. Cell. Neurosci. 12: 323, https://doi.org/10.3389/fncel.2018.00323.Search in Google Scholar PubMed PubMed Central
Tan, R.H., Ke, Y.D., Ittner, L.M., and Halliday, G.M. (2017). ALS/FTLD: experimental models and reality. Acta Neuropathol. 133: 177–196, https://doi.org/10.1007/s00401-016-1666-6.Search in Google Scholar PubMed
Tang, B.L. (2018). Promoting axonal regeneration through exosomes: an update of recent findings on exosomal PTEN and mTOR modifiers. Brain Res. Bull. 143: 123–131, https://doi.org/10.1016/j.brainresbull.2018.10.008.Search in Google Scholar PubMed
Tay, T.L., Mai, D., Dautzenberg, J., Fernandez-Klett, F., Lin, G., Sagar, Datta, M., Drougard, A., Stempfl, T., Ardura-Fabregat, A., et al.. (2017). A new fate mapping system reveals context-dependent random or clonal expansion of microglia. Nat. Neurosci. 20: 793–803, https://doi.org/10.1038/nn.4547.Search in Google Scholar PubMed
Tkach, M. and Thery, C. (2016). Communication by extracellular vesicles: where we are and where we need to go. Cell 164: 1226–1232, https://doi.org/10.1016/j.cell.2016.01.043.Search in Google Scholar PubMed
Trotta, T., Panaro, M.A., Cianciulli, A., Mori, G., Di Benedetto, A., and Porro, C. (2018). Microglia-derived extracellular vesicles in Alzheimer’s Disease: a double-edged sword. Biochem. Pharmacol. 148: 184–192, https://doi.org/10.1016/j.bcp.2017.12.020.Search in Google Scholar PubMed
Trotta, T., Panaro, M.A., Prifti, E., and Porro, C. (2019). Modulation of biological activities in glioblastoma mediated by curcumin. Nutr. Canc. 71: 1241–1253, https://doi.org/10.1080/01635581.2019.1604978.Search in Google Scholar PubMed
van Niel, G., D’Angelo, G., and Raposo, G. (2018). Shedding light on the cell biology of extracellular vesicles. Nat. Rev. Mol. Cell Biol. 19: 213–228, https://doi.org/10.1038/nrm.2017.125.Search in Google Scholar PubMed
Vandendriessche, C., Bruggeman, A., Van Cauwenberghe, C., and Vandenbroucke, R.E. (2020). Extracellular vesicles in alzheimer’s and Parkinson’s disease: small entities with large consequences. Cells 9, https://doi.org/10.3390/cells9112485.Search in Google Scholar PubMed PubMed Central
Vasek, M.J., Garber, C., Dorsey, D., Durrant, D.M., Bollman, B., Soung, A., Yu, J., Perez-Torres, C., Frouin, A., Wilton, D.K., et al.. (2016). A complement-microglial axis drives synapse loss during virus-induced memory impairment. Nature 534: 538–543, https://doi.org/10.1038/nature18283.Search in Google Scholar PubMed PubMed Central
Vassileff, N., Cheng, L., and Hill, A.F. (2020). Extracellular vesicles - propagators of neuropathology and sources of potential biomarkers and therapeutics for neurodegenerative diseases. J. Cell Sci. 133, https://doi.org/10.1242/jcs.243139.Search in Google Scholar PubMed
Venturini, A., Passalacqua, M., Pelassa, S., Pastorino, F., Tedesco, M., Cortese, K., Gagliani, M.C., Leo, G., Maura, G., Guidolin, D., et al.. (2019). Exosomes from astrocyte processes: signaling to neurons. Front. Pharmacol. 10: 1452, https://doi.org/10.3389/fphar.2019.01452.Search in Google Scholar PubMed PubMed Central
Verderio, C., Cagnoli, C., Bergami, M., Francolini, M., Schenk, U., Colombo, A., Riganti, L., Frassoni, C., Zuccaro, E., Danglot, L., et al.. (2012). TI-VAMP/VAMP7 is the SNARE of secretory lysosomes contributing to ATP secretion from astrocytes. Biol. Cell. 104: 213–228, https://doi.org/10.1111/boc.201100070.Search in Google Scholar PubMed
Verkhratsky, A., Matteoli, M., Parpura, V., Mothet, J.P., and Zorec, R. (2016). Astrocytes as secretory cells of the central nervous system: idiosyncrasies of vesicular secretion. EMBO J. 35: 239–257, https://doi.org/10.15252/embj.201592705.Search in Google Scholar PubMed PubMed Central
Winkler, C.W., Taylor, K.G., and Peterson, K.E. (2014). Location is everything: let-7b microRNA and TLR7 signaling results in a painful TRP. Sci. Signal. 7: 37, https://doi.org/10.1126/scisignal.2005407.Search in Google Scholar PubMed
Wang, G., Dinkins, M., He, Q., Zhu, G., Poirier, C., Campbell, A., Mayer-Proschel, M., and Bieberich, E. (2012). Astrocytes secrete exosomes enriched with proapoptotic ceramide and prostate apoptosis response 4 (PAR-4): potential mechanism of apoptosis induction in Alzheimer disease (AD). J. Biol. Chem. 287: 21384–21395, https://doi.org/10.1074/jbc.m112.340513.Search in Google Scholar
Watson, L.S., Hamlett, E.D., Stone, T.D., and Sims-Robinson, C. (2019). Neuronally derived extracellular vesicles: an emerging tool for understanding Alzheimer’s disease. Mol. Neurodegener. 14: 22, https://doi.org/10.1186/s13024-019-0317-5.Search in Google Scholar PubMed PubMed Central
Weng, Q., Wang, J., Wang, J., He, D., Cheng, Z., Zhang, F., Verma, R., Xu, L., Dong, X., Liao, Y., et al.. (2019). Single-cell transcriptomics uncovers glial progenitor diversity and cell fate determinants during development and gliomagenesis. Cell Stem Cell 24: 707–723, e708, https://doi.org/10.1016/j.stem.2019.03.006.Search in Google Scholar PubMed PubMed Central
Winston, C.N., Goetzl, E.J., Schwartz, J.B., Elahi, F.M., and Rissman, R.A. (2019). Complement protein levels in plasma astrocyte-derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer’s disease dementia. Alzheimer’s Dementia 11: 61–66, https://doi.org/10.1016/j.dadm.2018.11.002.Search in Google Scholar PubMed PubMed Central
Wu, Y., Dissing-Olesen, L., MacVicar, B.A., and Stevens, B. (2015). Microglia: dynamic mediators of synapse development and plasticity. Trends Immunol. 36: 605–613, https://doi.org/10.1016/j.it.2015.08.008.Search in Google Scholar PubMed PubMed Central
Xia, X., Wang, Y., Huang, Y., Zhang, H., Lu, H., and Zheng, J.C. (2019). Exosomal miRNAs in central nervous system diseases: biomarkers, pathological mediators, protective factors and therapeutic agents. Prog. Neurobiol. 183: 101694, https://doi.org/10.1016/j.pneurobio.2019.101694.Search in Google Scholar PubMed PubMed Central
Xiao, B., Chai, Y., Lv, S., Ye, M., Wu, M., Xie, L., Fan, Y., Zhu, X., and Gao, Z. (2017). Endothelial cell-derived exosomes protect SH-SY5Y nerve cells against ischemia/reperfusion injury. Int. J. Mol. Med. 40: 1201–1209, https://doi.org/10.3892/ijmm.2017.3106.Search in Google Scholar PubMed PubMed Central
Xin, H., Wang, F., Li, Y., Lu, Q.E., Cheung, W.L., Zhang, Y., Zhang, Z.G., and Chopp, M. (2017). Secondary release of exosomes from astrocytes contributes to the increase in neural plasticity and improvement of functional recovery after stroke in rats treated with exosomes harvested from MicroRNA 133b-overexpressing multipotent mesenchymal stromal cells. Cell Transplant. 26: 243–257, https://doi.org/10.3727/096368916x693031.Search in Google Scholar PubMed PubMed Central
Xu, L., Cao, H., Xie, Y., Zhang, Y., Du, M., Xu, X., Ye, R., and Liu, X. (2019). Exosome-shuttled miR-92b-3p from ischemic preconditioned astrocytes protects neurons against oxygen and glucose deprivation. Brain Res. 1717: 66–73, https://doi.org/10.1016/j.brainres.2019.04.009.Search in Google Scholar PubMed
Yanez-Mo, M., Siljander, P.R., Andreu, Z., Zavec, A.B., Borras, F.E., Buzas, E.I., Buzas, K., Casal, E., Cappello, F., Carvalho, J., et al.. (2015). Biological properties of extracellular vesicles and their physiological functions. J. Extracell. Vesicles 4: 27066, https://doi.org/10.3402/jev.v4.27066.Search in Google Scholar PubMed PubMed Central
You, Y. and Ikezu, T. (2019). Emerging roles of extracellular vesicles in neurodegenerative disorders. Neurobiol. Dis. 130: 104512, https://doi.org/10.1016/j.nbd.2019.104512.Search in Google Scholar PubMed PubMed Central
Yu, T., Wang, X., Zhi, T., Zhang, J., Wang, Y., Nie, E., Zhou, F., You, Y., and Liu, N. (2018). Delivery of MGMT mRNA to glioma cells by reactive astrocyte-derived exosomes confers a temozolomide resistance phenotype. Canc. Lett. 433: 210–220, https://doi.org/10.1016/j.canlet.2018.06.041.Search in Google Scholar PubMed
Yuyama, K. and Igarashi, Y. (2016). Physiological and pathological roles of exosomes in the nervous system. Biomol. Concepts 7: 53–68, https://doi.org/10.1515/bmc-2015-0033.Search in Google Scholar PubMed
Yuyama, K. and Igarashi, Y. (2017). Exosomes as carriers of alzheimer’s amyloid-ss. Front. Neurosci. 11: 229, https://doi.org/10.3389/fnins.2017.00229.Search in Google Scholar PubMed PubMed Central
Yuyama, K., Sun, H., Sakai, S., Mitsutake, S., Okada, M., Tahara, H., Furukawa, J., Fujitani, N., Shinohara, Y., and Igarashi, Y. (2014). Decreased amyloid-beta pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice. J. Biol. Chem. 289: 24488–24498, https://doi.org/10.1074/jbc.m114.577213.Search in Google Scholar
Zamanian, J.L., Xu, L., Foo, L.C., Nouri, N., Zhou, L., Giffard, R.G., and Barres, B.A. (2012). Genomic analysis of reactive astrogliosis. J. Neurosci. 32: 6391–6410, https://doi.org/10.1523/jneurosci.6221-11.2012.Search in Google Scholar PubMed PubMed Central
Zhang, X., Abels, E.R., Redzic, J.S., Margulis, J., Finkbeiner, S., and Breakefield, X.O. (2016). Potential transfer of polyglutamine and CAG-repeat RNA in extracellular vesicles in huntington’s disease: background and evaluation in cell culture. Cell. Mol. Neurobiol. 36: 459–470, https://doi.org/10.1007/s10571-016-0350-7.Search in Google Scholar PubMed PubMed Central
Zhang, Z.G. and Chopp, M. (2016). Exosomes in stroke pathogenesis and therapy. J. Clin. Invest. 126: 1190–1197, https://doi.org/10.1172/jci81133.Search in Google Scholar
Zondler, L., Feiler, M.S., Freischmidt, A., Ruf, W.P., Ludolph, A.C., Danzer, K.M., and Weishaupt, J.H. (2017). Impaired activation of ALS monocytes by exosomes. Immunol. Cell Biol. 95: 207–214, https://doi.org/10.1038/icb.2016.89.Search in Google Scholar PubMed
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