REFERENCES
1. Wolf P. The nature and significance of platelet products in human plasma. Br J Haematol 1967;13:269-88.
2. Zhang Y, Liu Y, Liu H, Tang WH. Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci 2019;9:19.
3. Cufaro MC, Pieragostino D, Lanuti P, et al. Extracellular Vesicles and Their Potential Use in Monitoring Cancer Progression and Therapy: The Contribution of Proteomics. J Oncol 2019;2019:1639854.
4. Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles 2018;7:1535750.
5. Trams EG, Lauter CJ, Norman Salem J, Heine U. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta 1981;645:63-70.
6. Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem 1987;262:9412-20.
7. Liu W, Bai X, Zhang A, Huang J, Xu S, Zhang J. Role of Exosomes in Central Nervous System Diseases. Front Mol Neurosci 2019;12:240.
9. Osier N, Motamedi V, Edwards K, et al. Exosomes in Acquired Neurological Disorders: New Insights into Pathophysiology and Treatment. Mol Neurobiol 2018;55:9280-93.
10. Saeedi S, Israel S, Nagy C, Turecki G. The emerging role of exosomes in mental disorders. Transl Psychiatry 2019;9:122.
11. Looze C, Yui D, Leung L, et al. Proteomic profiling of human plasma exosomes identifies PPARgamma as an exosome-associated protein. Biochem Biophys Res Commun 2009;378:433-8.
12. Street JM, Barran PE, Mackay CL, et al. Identification and proteomic profiling of exosomes in human cerebrospinal fluid. J Transl Med 2012;10:5.
13. Michael A, Bajracharya SD, Yuen PS, et al. Exosomes from human saliva as a source of microRNA biomarkers. Oral Dis 2010;16:34-8.
14. Gonzales PA, Pisitkun T, Hoffert JD, et al. Large-scale proteomics and phosphoproteomics of urinary exosomes. J Am Soc Nephrol 2009;20:363-79.
15. Admyre C, Johansson SM, Qazi KR, et al. Exosomes with immune modulatory features are present in human breast milk. J Immunol 2007;179:1969-78.
16. Cañas JA, Sastre B, Rodrigo-Muñoz JM, Del Pozo V. Exosomes: A new approach to asthma pathology. Clin Chim Acta 2019;495:139-47.
17. Zhang X, Yuan X, Shi H, Wu L, Qian H, Xu W. Exosomes in cancer: small particle, big player. J Hematol Oncol 2015;8:83.
18. Huang X, Yuan T, Tschannen M, et al. Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genomics 2013;14:319.
19. Hewson C, Capraro D, Burdach J, Whitaker N, Morris KV. Extracellular vesicle associated long non-coding RNAs functionally enhance cell viability. Noncoding RNA Res 2016;1:3-11.
20. Soria FN, Pampliega O, Bourdenx M, Meissner WG, Bezard E, Dehay B. Exosomes, an Unmasked Culprit in Neurodegenerative Diseases. Front Neurosci 2017;11:26.
21. Sahu R, Kaushik S, Clement CC, et al. Microautophagy of cytosolic proteins by late endosomes. Dev Cell 2011;20:131-9.
22. Record M. Intercellular communication by exosomes in placenta: a possible role in cell fusion? Placenta 2014;35:297-302.
23. Hessvik NP, Llorente A. Current knowledge on exosome biogenesis and release. Cell Mol Life Sci 2018;75:193-208.
24. Colombo M, Moita C, van Niel G, et al. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J Cell Sci 2013;126:5553-65.
26. Baietti MF, Zhang Z, Mortier E, et al. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol 2012;14:677-85.
28. Stuffers S, Sem Wegner C, Stenmark H, Brech A. Multivesicular endosome biogenesis in the absence of ESCRTs. Traffic 2009;10:925-37.
29. Escola JM, Kleijmeer MJ, Stoorvogel W, Griffith JM, Yoshie O, Geuze HJ. Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem 1998;273:20121-7.
30. Chairoungdua A, Smith DL, Pochard P, Hull M, Caplan MJ. Exosome release of β-catenin: a novel mechanism that antagonizes Wnt signaling. J Cell Biol 2010;190:1079-91.
31. Nazarenko I, Rana S, Baumann A, et al. Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation. Cancer Res 2010;70:1668-78.
32. Hurwitz SN, Conlon MM, Rider MA, Brownstein NC, Meckes DG Jr. Nanoparticle analysis sheds budding insights into genetic drivers of extracellular vesicle biogenesis. J Extracell Vesicles 2016;5:31295.
33. den Boorn JG, Dassler J, Coch C, Schlee M, Hartmann G. Exosomes as nucleic acid nanocarriers. Adv Drug Deliv Rev 2013;65:331-5.
34. Castro BM, Prieto M, Silva LC. Ceramide: a simple sphingolipid with unique biophysical properties. Prog Lipid Res 2014;54:53-67.
35. Ostrowski M, Carmo NB, Krumeich S, et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 2010;12:19-30; sup pp 1.
36. Hsu C, Morohashi Y, Yoshimura S, et al. Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C. J Cell Biol 2010;189:223-32.
37. Savina A, Furlán M, Vidal M, Colombo MI. Exosome release is regulated by a calcium-dependent mechanism in K562 cells. J Biol Chem 2003;278:20083-90.
38. Parolini I, Federici C, Raggi C, et al. Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem 2009;284:34211-22.
39. Lehmann BD, Paine MS, Brooks AM, et al. Senescence-associated exosome release from human prostate cancer cells. Cancer Res 2008;68:7864-71.
40. Beer L, Zimmermann M, Mitterbauer A, et al. Analysis of the Secretome of Apoptotic Peripheral Blood Mononuclear Cells: Impact of Released Proteins and Exosomes for Tissue Regeneration. Sci Rep 2015;5:16662.
41. Xiao X, Yu S, Li S, et al. Exosomes: decreased sensitivity of lung cancer A549 cells to cisplatin. PLoS One 2014;9:e89534.
42. King HW, Michael MZ, Gleadle JM. Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer 2012;12:421.
43. Kanemoto S, Nitani R, Murakami T, et al. Multivesicular body formation enhancement and exosome release during endoplasmic reticulum stress. Biochem Biophys Res Commun 2016;480:166-72.
44. Miyanishi M, Tada K, Koike M, Uchiyama Y, Kitamura T, Nagata S. Identification of Tim4 as a phosphatidylserine receptor. Nature 2007;450:435-9.
45. Segura E, Nicco C, Lombard B, et al. ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming. Blood 2005;106:216-23.
46. Feng D, Zhao WL, Ye YY, et al. Cellular internalization of exosomes occurs through phagocytosis. Traffic 2010;11:675-87.
47. Fitzner D, Schnaars M, van Rossum D, et al. Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis. J Cell Sci 2011;124:447-58.
48. Frühbeis C, Fröhlich D, Krämer-Albers EM. Emerging roles of exosomes in neuron-glia communication. Front Physiol 2012;3:119.
49. Guitart K, Loers G, Buck F, Bork U, Schachner M, Kleene R. Improvement of neuronal cell survival by astrocyte-derived exosomes under hypoxic and ischemic conditions depends on prion protein. Glia 2016;64:896-910.
50. Chivet M, Javalet C, Laulagnier K, Blot B, Hemming FJ, Sadoul R. Exosomes secreted by cortical neurons upon glutamatergic synapse activation specifically interact with neurons. J Extracell Vesicles 2014;3:24722.
51. Gurunathan S, Kang MH, Jeyaraj M, Qasim M, Kim JH. Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes. Cells 2019;8:307.
52. Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L. Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int 2010;78:838-48.
53. Gurunathan S, Kang MH, Kim JH. A Comprehensive Review on Factors Influences Biogenesis, Functions, Therapeutic and Clinical Implications of Exosomes. Int J Nanomedicine 2021;16:1281-312.
54. Lachenal G, Pernet-Gallay K, Chivet M, et al. Release of exosomes from differentiated neurons and its regulation by synaptic glutamatergic activity. Mol Cell Neurosci 2011;46:409-18.
55. Bakhti M, Winter C, Simons M. Inhibition of myelin membrane sheath formation by oligodendrocyte-derived exosome-like vesicles. J Biol Chem 2011;286:787-96.
56. Edgar JM, Nave KA. The role of CNS glia in preserving axon function. Curr Opin Neurobiol 2009;19:498-504.
57. Tytell M, Greenberg S, Lasek R. Heat shock-like protein is transferred from glia to axon. Brain Research 1986;363:161-4.
58. Tytell M. Release of heat shock proteins (Hsps) and the effects of extracellular Hsps on neural cells and tissues. Int J Hyperthermia 2005;21:445-55.
59. Fauré J, Lachenal G, Court M, et al. Exosomes are released by cultured cortical neurones. Mol Cell Neurosci 2006;31:642-8.
60. Ghidoni R, Paterlini A, Albertini V, et al. Cystatin C is released in association with exosomes: a new tool of neuronal communication which is unbalanced in Alzheimer's disease. Neurobiol Aging 2011;32:1435-42.
61. Korkut C, Li Y, Koles K, et al. Regulation of postsynaptic retrograde signaling by presynaptic exosome release. Neuron 2013;77:1039-46.
62. Bahrini I, Song JH, Diez D, Hanayama R. Neuronal exosomes facilitate synaptic pruning by up-regulating complement factors in microglia. Sci Rep 2015;5:7989.
63. Morel L, Regan M, Higashimori H, et al. Neuronal exosomal miRNA-dependent translational regulation of astroglial glutamate transporter GLT1. J Biol Chem 2013;288:7105-16.
64. Wang S, Cesca F, Loers G, et al. Synapsin I is an oligomannose-carrying glycoprotein, acts as an oligomannose-binding lectin, and promotes neurite outgrowth and neuronal survival when released via glia-derived exosomes. J Neurosci 2011;31:7275-90.
65. Prada I, Gabrielli M, Turola E, et al. Glia-to-neuron transfer of miRNAs via extracellular vesicles: a new mechanism underlying inflammation-induced synaptic alterations. Acta Neuropathol 2018;135:529-50.
66. Yamada J, Jinno S. Promotion of synaptogenesis and neural circuit development by exosomes. Ann Transl Med 2019;7:S323.
67. Feliciano DM, Zhang S, Nasrallah CM, Lisgo SN, Bordey A. Embryonic cerebrospinal fluid nanovesicles carry evolutionarily conserved molecules and promote neural stem cell amplification. PLoS One 2014;9:e88810.
68. Bátiz LF, Castro MA, Burgos PV, et al. Exosomes as Novel Regulators of Adult Neurogenic Niches. Front Cell Neurosci 2015;9:501.
69. Ma Y, Li C, Huang Y, Wang Y, Xia X, Zheng JC. Exosomes released from neural progenitor cells and induced neural progenitor cells regulate neurogenesis through miR-21a. Cell Commun Signal 2019;17:96.
70. Sharma P, Mesci P, Carromeu C, et al. Exosomes regulate neurogenesis and circuit assembly. Proc Natl Acad Sci U S A 2019;116:16086-94.
71. Perets N, Oron O, Herman S, Elliott E, Offen D. Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mouse model of autism Shank3B. Mol Autism 2020;11:65.
72. Elsharkasy OM, Nordin JZ, Hagey DW, et al. Extracellular vesicles as drug delivery systems: Why and how? Adv Drug Deliv Rev 2020;159:332-43.
73. Gee P, Lung MSY, Okuzaki Y, et al. Extracellular nanovesicles for packaging of CRISPR-Cas9 protein and sgRNA to induce therapeutic exon skipping. Nat Commun 2020;11:1334.
74. Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology 2013;80:1778-83.
76. Reza-Zaldivar EE, Hernández-Sapiéns MA, Minjarez B, Gutiérrez-Mercado YK, Márquez-Aguirre AL, Canales-Aguirre AA. Potential Effects of MSC-Derived Exosomes in Neuroplasticity in Alzheimer's Disease. Front Cell Neurosci 2018;12:317.
77. Xiao T, Zhang W, Jiao B, Pan CZ, Liu X, Shen L. The role of exosomes in the pathogenesis of Alzheimer' disease. Transl Neurodegener 2017;6:3.
78. DeLeo AM, Ikezu T. Extracellular Vesicle Biology in Alzheimer's Disease and Related Tauopathy. J Neuroimmune Pharmacol 2018;13:292-308.
79. Pérez M, Avila J, Hernández F. Propagation of Tau via Extracellular Vesicles. Front Neurosci 2019;13:698.
80. Podvin S, Jones A, Liu Q, et al. Dysregulation of Exosome Cargo by Mutant Tau Expressed in Human-induced Pluripotent Stem Cell (iPSC) Neurons Revealed by Proteomics Analyses. Mol Cell Proteomics 2020;19:1017-34.
81. Yuyama K, Sun H, Mitsutake S, Igarashi Y. Sphingolipid-modulated exosome secretion promotes clearance of amyloid-β by microglia. J Biol Chem 2012;287:10977-89.
82. Yuyama K, Sun H, Sakai S, et al. Decreased amyloid-β pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice. J Biol Chem 2014;289:24488-98.
83. An K, Klyubin I, Kim Y, et al. Exosomes neutralize synaptic-plasticity-disrupting activity of Aβ assemblies in vivo. Mol Brain 2013;6:47.
84. Falker C, Hartmann A, Guett I, et al. Exosomal cellular prion protein drives fibrillization of amyloid beta and counteracts amyloid beta-mediated neurotoxicity. J Neurochem 2016;137:88-100.
85. Yuyama K, Sun H, Usuki S, et al. A potential function for neuronal exosomes: sequestering intracerebral amyloid-β peptide. FEBS Lett 2015;589:84-8.
86. Katsuda T, Tsuchiya R, Kosaka N, et al. Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes. Sci Rep 2013;3:1197.
87. Bulloj A, Leal MC, Xu H, Castaño EM, Morelli L. Insulin-degrading enzyme sorting in exosomes: a secretory pathway for a key brain amyloid-beta degrading protease. J Alzheimers Dis 2010;19:79-95.
88. Langui D, Girardot N, El Hachimi KH, et al. Subcellular Topography of Neuronal Aβ Peptide in APPxPS1 Transgenic Mice. Am J Pathol 2004;165:1465-77.
89. Rajendran L, Honsho M, Zahn TR, et al. Alzheimer's disease beta-amyloid peptides are released in association with exosomes. Proc Natl Acad Sci U S A 2006;103:11172-7.
90. Vingtdeux V, Hamdane M, Loyens A, et al. Alkalizing drugs induce accumulation of amyloid precursor protein by-products in luminal vesicles of multivesicular bodies. J Biol Chem 2007;282:18197-205.
91. Sullivan CP, Jay AG, Stack EC, et al. Retromer disruption promotes amyloidogenic APP processing. Neurobiol Dis 2011;43:338-45.
92. Dinkins MB, Dasgupta S, Wang G, Zhu G, Bieberich E. Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer's disease. Neurobiol Aging 2014;35:1792-800.
93. Dinkins MB, Dasgupta S, Wang G, et al. The 5XFAD Mouse Model of Alzheimer's Disease Exhibits an Age-Dependent Increase in Anti-Ceramide IgG and Exogenous Administration of Ceramide Further Increases Anti-Ceramide Titers and Amyloid Plaque Burden. J Alzheimers Dis 2015;46:55-61.
94. Bellingham SA, Guo BB, Coleman BM, Hill AF. Exosomes: vehicles for the transfer of toxic proteins associated with neurodegenerative diseases? Front Physiol 2012;3:124.
95. Bolmont T, Haiss F, Eicke D, et al. Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance. J Neurosci 2008;28:4283-92.
96. Hickman SE, Allison EK, El Khoury J. Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer's disease mice. J Neurosci 2008;28:8354-60.
97. Song Z, Xu Y, Deng W, et al. Brain Derived Exosomes Are a Double-Edged Sword in Alzheimer's Disease. Front Mol Neurosci 2020;13:79.
98. Trotta T, Panaro MA, Cianciulli A, Mori G, Di Benedetto A, Porro C. Microglia-derived extracellular vesicles in Alzheimer's Disease: A double-edged sword. Biochem Pharmacol 2018;148:184-92.
99. Saman S, Kim W, Raya M, et al. Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease. J Biol Chem 2012;287:3842-9.
100. Guix FX, Corbett GT, Cha DJ, et al. Detection of Aggregation-Competent Tau in Neuron-Derived Extracellular Vesicles. Int J Mol Sci 2018;19:663.
101. Asai H, Ikezu S, Tsunoda S, et al. Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat Neurosci 2015;18:1584-93.
102. Fiandaca MS, Kapogiannis D, Mapstone M, et al. Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study. Alzheimers Dement 2015;11:600-7.e1.
103. Goetzl EJ, Mustapic M, Kapogiannis D, et al. Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer's disease. FASEB J 2016;30:3853-9.
104. Zhuang X, Xiang X, Grizzle W, et al. Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther 2011;19:1769-79.
106. Olanow CW, Brundin P. Parkinson's disease and alpha synuclein: is Parkinson's disease a prion-like disorder? Mov Disord 2013;28:31-40.
107. Emmanouilidou E, Melachroinou K, Roumeliotis T, et al. Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J Neurosci 2010;30:6838-51.
108. Lee HJ, Patel S, Lee SJ. Intravesicular localization and exocytosis of alpha-synuclein and its aggregates. J Neurosci 2005;25:6016-24.
109. Alvarez-Erviti L, Seow Y, Schapira AH, et al. Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission. Neurobiol Dis 2011;42:360-7.
110. Cabin DE, Shimazu K, Murphy D, et al. Synaptic Vesicle Depletion Correlates with Attenuated Synaptic Responses to Prolonged Repetitive Stimulation in Mice Lacking α-Synuclein. J Neurosci 2002;22:8797-807.
111. Gedalya T, Loeb V, Israeli E, Altschuler Y, Selkoe DJ, Sharon R. Alpha-synuclein and polyunsaturated fatty acids promote clathrin-mediated endocytosis and synaptic vesicle recycling. Traffic 2009;10:218-34.
112. Grey M, Dunning CJ, Gaspar R, et al. Acceleration of α-synuclein aggregation by exosomes. J Biol Chem 2015;290:2969-82.
113. Stuendl A, Kunadt M, Kruse N, et al. Induction of α-synuclein aggregate formation by CSF exosomes from patients with Parkinson's disease and dementia with Lewy bodies. Brain 2016;139:481-94.
114. Danzer KM, Kranich LR, Ruf WP, et al. Exosomal cell-to-cell transmission of alpha synuclein oligomers. Mol Neurodegener 2012;7:42.
115. Hornung S, Dutta S, Bitan G. CNS-Derived Blood Exosomes as a Promising Source of Biomarkers: Opportunities and Challenges. Front Mol Neurosci 2020;13:38.
116. Shi M, Liu C, Cook TJ, et al. Plasma exosomal α-synuclein is likely CNS-derived and increased in Parkinson's disease. Acta Neuropathol 2014;128:639-50.
117. Si X, Tian J, Chen Y, Yan Y, Pu J, Zhang B. Central Nervous System-Derived Exosomal Alpha-Synuclein in Serum May Be a Biomarker in Parkinson's Disease. Neuroscience 2019;413:308-16.
118. Jiang C, Hopfner F, Katsikoudi A, et al. Serum neuronal exosomes predict and differentiate Parkinson's disease from atypical parkinsonism. J Neurol Neurosurg Psychiatry 2020;91:720-9.
119. Niu M, Li Y, Li G, et al. A longitudinal study on α-synuclein in plasma neuronal exosomes as a biomarker for Parkinson's disease development and progression. Eur J Neurol 2020;27:967-74.
120. Haney MJ, Klyachko NL, Zhao Y, et al. Exosomes as drug delivery vehicles for Parkinson's disease therapy. J Control Release 2015;207:18-30.
121. Chen HX, Liang FC, Gu P, et al. Exosomes derived from mesenchymal stem cells repair a Parkinson's disease model by inducing autophagy. Cell Death Dis 2020;11:288.
122. Qu M, Lin Q, Huang L, et al. Dopamine-loaded blood exosomes targeted to brain for better treatment of Parkinson's disease. J Control Release 2018;287:156-66.
123. Bonda DJ, Manjila S, Mehndiratta P, et al. Human prion diseases: surgical lessons learned from iatrogenic prion transmission. Neurosurg Focus 2016;41:E10.
124. Fevrier B, Vilette D, Archer F, et al. Cells release prions in association with exosomes. Proc Natl Acad Sci U S A 2004;101:9683-8.
125. Alais S, Simoes S, Baas D, et al. Mouse neuroblastoma cells release prion infectivity associated with exosomal vesicles. Biol Cell 2008;100:603-15.
126. Vilette D, Laulagnier K, Huor A, et al. Efficient inhibition of infectious prions multiplication and release by targeting the exosomal pathway. Cell Mol Life Sci 2015;72:4409-27.
127. Guo BB, Bellingham SA, Hill AF. Stimulating the Release of Exosomes Increases the Intercellular Transfer of Prions. J Biol Chem 2016;291:5128-37.
128. Vella LJ, Sharples RA, Lawson VA, Masters CL, Cappai R, Hill AF. Packaging of prions into exosomes is associated with a novel pathway of PrP processing. J Pathol 2007;211:582-90.
129. Cervenakova L, Saá P, Yakovleva O, et al. Are prions transported by plasma exosomes? Transfus Apher Sci 2016;55:70-83.
130. Cheng L, Zhao W, Hill AF. Exosomes and their role in the intercellular trafficking of normal and disease associated prion proteins. Mol Aspects Med 2018;60:62-8.
133. Prasad A, Bharathi V, Sivalingam V, Girdhar A, Patel BK. Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis. Front Mol Neurosci 2019;12:25.
134. Zondler L, Feiler MS, Freischmidt A, et al. Impaired activation of ALS monocytes by exosomes. Immunol Cell Biol 2017;95:207-14.
135. Grad LI, Pokrishevsky E, Silverman JM, Cashman NR. Exosome-dependent and independent mechanisms are involved in prion-like transmission of propagated Cu/Zn superoxide dismutase misfolding. Prion 2014;8:331-5.
136. Iguchi Y, Eid L, Parent M, et al. Exosome secretion is a key pathway for clearance of pathological TDP-43. Brain 2016;139:3187-201.
137. Chen PC, Wu D, Hu CJ, Chen HY, Hsieh YC, Huang CC. Exosomal TAR DNA-binding protein-43 and neurofilaments in plasma of amyotrophic lateral sclerosis patients: A longitudinal follow-up study. J Neurol Sci 2020;418:117070.
138. Calabria E, Scambi I, Bonafede R, et al. ASCs-Exosomes Recover Coupling Efficiency and Mitochondrial Membrane Potential in an. in vitro ;13:1070.
139. Pagan F, Torres-yaghi Y, Altshuler M. The diagnosis and natural history of Huntington disease. Handb Clin Neurol 2017;144:63-7.
140. Wang JKT, Langfelder P, Horvath S, Palazzolo MJ. Exosomes and Homeostatic Synaptic Plasticity Are Linked to Each other and to Huntington's, Parkinson's, and Other Neurodegenerative Diseases by Database-Enabled Analyses of Comprehensively Curated Datasets. Front Neurosci 2017;11:149.
141. Jeon I, Cicchetti F, Cisbani G, et al. Human-to-mouse prion-like propagation of mutant huntingtin protein. Acta Neuropathol 2016;132:577-92.
142. Zhang X, Abels ER, Redzic JS, Margulis J, Finkbeiner S, Breakefield XO. Potential Transfer of Polyglutamine and CAG-Repeat RNA in Extracellular Vesicles in Huntington's Disease: Background and Evaluation in Cell Culture. Cell Mol Neurobiol 2016;36:459-70.
143. Díez-Planelles C, Sánchez-Lozano P, Crespo MC, et al. Circulating microRNAs in Huntington's disease: Emerging mediators in metabolic impairment. Pharmacol Res 2016;108:102-10.
144. Kumar S, Vijayan M, Bhatti J, Reddy P. MicroRNAs as Peripheral Biomarkers in Aging and Age-Related Diseases. Prog Mol Biol Transl Sci 2017;146:47-94.
145. Lee ST, Im W, Ban JJ, et al. Exosome-Based Delivery of miR-124 in a Huntington's Disease Model. J Mov Disord 2017;10:45-52.
146. Didiot MC, Hall LM, Coles AH, et al. Exosome-mediated Delivery of Hydrophobically Modified siRNA for Huntingtin mRNA Silencing. Mol Ther 2016;24:1836-47.
149. Batool A, Hill TDM, Nguyen NT, et al. Altered Biogenesis and MicroRNA Content of Hippocampal Exosomes Following Experimental Status Epilepticus. Front Neurosci 2019;13:1404.
150. Gitaí DLG, Dos Santos YDR, Upadhya R, Kodali M, Madhu LN, Shetty AK. Extracellular Vesicles in the Forebrain Display Reduced miR-346 and miR-331-3p in a Rat Model of Chronic Temporal Lobe Epilepsy. Mol Neurobiol 2020;57:1674-87.
151. Yan S, Zhang H, Xie W, et al. Altered microRNA profiles in plasma exosomes from mesial temporal lobe epilepsy with hippocampal sclerosis. Oncotarget 2017;8:4136-46.
152. Chen SD, Pan HY, Huang JB, et al. Circulating MicroRNAs from Serum Exosomes May Serve as a Putative Biomarker in the Diagnosis and Treatment of Patients with Focal Cortical Dysplasia. Cells 2020;9:1867.
153. Long Q, Upadhya D, Hattiangady B, et al. Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus. Proc Natl Acad Sci U S A 2017;114:E3536-45.
155. Galazka G, Mycko MP, Selmaj I, Raine CS, Selmaj KW. Multiple sclerosis: Serum-derived exosomes express myelin proteins. Mult Scler 2018;24:449-58.
156. Pieragostino D, Cicalini I, Lanuti P, et al. Enhanced release of acid sphingomyelinase-enriched exosomes generates a lipidomics signature in CSF of Multiple Sclerosis patients. Sci Rep 2018;8:3071.
157. Kimura K, Hohjoh H, Fukuoka M, et al. Circulating exosomes suppress the induction of regulatory T cells via let-7i in multiple sclerosis. Nat Commun 2018;9:17.
158. Selmaj I, Cichalewska M, Namiecinska M, et al. Global exosome transcriptome profiling reveals biomarkers for multiple sclerosis. Ann Neurol 2017;81:703-17.
159. Ebrahimkhani S, Vafaee F, Young PE, et al. Exosomal microRNA signatures in multiple sclerosis reflect disease status. Sci Rep 2017;7:14293.
160. Manna I, Iaccino E, Dattilo V, et al. Exosome-associated miRNA profile as a prognostic tool for therapy response monitoring in multiple sclerosis patients. FASEB J 2018;32:4241-6.
161. Wei Z, Fan B, Ding H, et al. Proteomics analysis of Schwann cell-derived exosomes: a novel therapeutic strategy for central nervous system injury. Mol Cell Biochem 2019;457:51-9.
162. Domingues HS, Falcão AM, Mendes-Pinto I, Salgado AJ, Teixeira FG. Exosome Circuitry During (De)(Re)Myelination of the Central Nervous System. Front Cell Dev Biol 2020;8:483.
163. Krämer-Albers EM, Bretz N, Tenzer S, et al. Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: Trophic support for axons? Proteomics Clin Appl 2007;1:1446-61.
164. Lopez-Verrilli MA, Picou F, Court FA. Schwann cell-derived exosomes enhance axonal regeneration in the peripheral nervous system. Glia 2013;61:1795-806.
165. Hu M, Hong L, Liu C, et al. Electrical stimulation enhances neuronal cell activity mediated by Schwann cell derived exosomes. Sci Rep 2019;9:4206.
166. Bucan V, Vaslaitis D, Peck CT, Strauß S, Vogt PM, Radtke C. Effect of Exosomes from Rat Adipose-Derived Mesenchymal Stem Cells on Neurite Outgrowth and Sciatic Nerve Regeneration After Crush Injury. Mol Neurobiol 2019;56:1812-24.
167. Xiao Y, Geng F, Wang G, Li X, Zhu J, Zhu W. Bone marrow-derived mesenchymal stem cells-derived exosomes prevent oligodendrocyte apoptosis through exosomal miR-134 by targeting caspase-8. J Cell Biochem ;2018:2109-18.
168. Thomi G, Joerger-Messerli M, Haesler V, Muri L, Surbek D, Schoeberlein A. Intranasally Administered Exosomes from Umbilical Cord Stem Cells Have Preventive Neuroprotective Effects and Contribute to Functional Recovery after Perinatal Brain Injury. Cells 2019;8:855.
169. Otero-Ortega L, Laso-García F, Gómez-de Frutos M, et al. Role of Exosomes as a Treatment and Potential Biomarker for Stroke. Transl Stroke Res 2019;10:241-9.
171. Xin H, Li Y, Buller B, et al. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells 2012;30:1556-64.
172. Chen F, Du Y, Esposito E, et al. Effects of Focal Cerebral Ischemia on Exosomal Versus Serum miR126. Transl Stroke Res 2015;6:478-84.
173. Yang J, Zhang X, Chen X, Wang L, Yang G. Exosome Mediated Delivery of miR-124 Promotes Neurogenesis after Ischemia. Mol Ther Nucleic Acids 2017;7:278-87.
174. Seifert HA, Offner H. The splenic response to stroke: from rodents to stroke subjects. J Neuroinflammation 2018;15:195.
175. Makin SD, Cook FA, Dennis MS, Wardlaw JM. Cerebral small vessel disease and renal function: systematic review and meta-analysis. Cerebrovasc Dis 2015;39:39-52.
176. Zhang G, Chen L, Guo X, et al. Comparative Analysis of microRNA Expression Profiles of Exosomes Derived from Normal and Hypoxic Preconditioning Human Neural Stem Cells by Next Generation Sequencing. J Biomed Nanotechnol 2018;14:1075-89.
177. Li DB, Liu JL, Wang W, et al. Plasma Exosomal miRNA-122-5p and miR-300-3p as Potential Markers for Transient Ischaemic Attack in Rats. Front Aging Neurosci 2018;10:24.
178. Datta A, Chen CP, Sze SK. Discovery of prognostic biomarker candidates of lacunar infarction by quantitative proteomics of microvesicles enriched plasma. PLoS One 2014;9:e94663.
179. Kanhai DA, de Kleijn DP, Kappelle LJ, et al. SMART Study Group. Extracellular vesicle protein levels are related to brain atrophy and cerebral white matter lesions in patients with manifest vascular disease: the SMART-MR study. BMJ Open 2014;4:e003824.
180. Ji Q, Ji Y, Peng J, et al. Increased Brain-Specific MiR-9 and MiR-124 in the Serum Exosomes of Acute Ischemic Stroke Patients. PLoS One 2016;11:e0163645.
181. Li DB, Liu JL, Wang W, et al. Plasma Exosomal miR-422a and miR-125b-2-3p Serve as Biomarkers for Ischemic Stroke. Curr Neurovasc Res 2017;14:330-7.
182. Chen Y, Song Y, Huang J, et al. Increased Circulating Exosomal miRNA-223 Is Associated with Acute Ischemic Stroke. Front Neurol 2017;8:57.
183. Wang W, Li DB, Li RY, et al. Diagnosis of Hyperacute and Acute Ischaemic Stroke: The Potential Utility of Exosomal MicroRNA-21-5p and MicroRNA-30a-5p. Cerebrovasc Dis 2018;45:204-12.
184. McKee CA, Lukens JR. Emerging Roles for the Immune System in Traumatic Brain Injury. Front Immunol 2016;7:556.
185. Taylor DD, Gercel-Taylor C. Exosome platform for diagnosis and monitoring of traumatic brain injury. Philos Trans R Soc Lond B Biol Sci 2014;369:20130503.
186. Huang S, Ge X, Yu J, et al. 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 2018;32:512-28.
187. Guedes VA, Kenney K, Shahim P, et al. CENC Multisite Observational Study Investigators. Exosomal neurofilament light: A prognostic biomarker for remote symptoms after mild traumatic brain injury? Neurology 2020;94:e2412-23.
188. Goetzl EJ, Elahi FM, Mustapic M, et al. Altered levels of plasma neuron-derived exosomes and their cargo proteins characterize acute and chronic mild traumatic brain injury. FASEB J 2019;33:5082-8.
189. Beard K, Meaney DF, Issadore D. Clinical Applications of Extracellular Vesicles in the Diagnosis and Treatment of Traumatic Brain Injury. J Neurotrauma 2020;37:2045-56.
190. Gruzdev SK, Yakovlev AA, Druzhkova TA, Guekht AB, Gulyaeva NV. The Missing Link: How Exosomes and miRNAs can Help in Bridging Psychiatry and Molecular Biology in the Context of Depression, Bipolar Disorder and Schizophrenia. Cell Mol Neurobiol 2019;39:729-50.
191. Baudry A, Mouillet-Richard S, Schneider B, Launay JM, Kellermann O. miR-16 targets the serotonin transporter: a new facet for adaptive responses to antidepressants. Science 2010;329:1537-41.
192. Beveridge NJ, Tooney PA, Carroll AP, et al. Dysregulation of miRNA 181b in the temporal cortex in schizophrenia. Hum Mol Genet 2008;17:1156-68.
193. Muiños-Gimeno M, Espinosa-Parrilla Y, Guidi M, et al. Human microRNAs miR-22, miR-138-2, miR-148a, and miR-488 are associated with panic disorder and regulate several anxiety candidate genes and related pathways. Biol Psychiatry 2011;69:526-33.
194. Rong H, Liu TB, Yang KJ, et al. MicroRNA-134 plasma levels before and after treatment for bipolar mania. J Psychiatr Res 2011;45:92-5.
195. Banigan MG, Kao PF, Kozubek JA, et al. Differential expression of exosomal microRNAs in prefrontal cortices of schizophrenia and bipolar disorder patients. PLoS One 2013;8:e48814.
196. Du Y, Yu Y, Hu Y, et al. Genome-Wide, Integrative Analysis Implicates Exosome-Derived MicroRNA Dysregulation in Schizophrenia. Schizophr Bull 2019;45:1257-66.
197. Lee ST, Chu K, Jung KH, et al. miR-206 regulates brain-derived neurotrophic factor in Alzheimer disease model. Ann Neurol 2012;72:269-77.
198. role of microRNAs in major depressive disorder: diagnosis and therapeutic implications. Dialogues Clin Neurosci 2014;16:43-61.
199. Liang JQ, Liao HR, Xu CX, et al. Serum Exosome-Derived miR-139-5p as a Potential Biomarker for Major Depressive Disorder. Neuropsychiatr Dis Treat 2020;16:2689-93.
200. Wen PY, Weller M, Lee EQ, et al. Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions. Neuro Oncol 2020;22:1073-113.
202. Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009;10:459-66.
203. Patel AP, Tirosh I, Trombetta JJ, et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 2014;344:1396-401.
204. Galli R, Binda E, Orfanelli U, et al. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 2004;64:7011-21.
205. Chen J, Li Y, Yu TS, et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 2012;488:522-6.
206. Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature 2004;432:396-401.
207. Oushy S, Hellwinkel JE, Wang M, et al. Glioblastoma multiforme-derived extracellular vesicles drive normal astrocytes towards a tumour-enhancing phenotype. Philos Trans R Soc Lond B Biol Sci 2018;373:20160477.
208. Gao X, Zhang Z, Mashimo T, et al. Gliomas Interact with Non-glioma Brain Cells via Extracellular Vesicles. Cell Rep 2020;30:2489-2500.e5.
209. Mondal A, Kumari Singh D, Panda S, Shiras A. Extracellular Vesicles As Modulators of Tumor Microenvironment and Disease Progression in Glioma. Front Oncol 2017;7:144.
210. Shao H, Chung J, Lee K, et al. Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma. Nat Commun 2015;6:6999.
211. Skog J, Würdinger T, van Rijn S, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 2008;10:1470-6.
212. Simon T, Jackson E, Giamas G. Breaking through the glioblastoma micro-environment via extracellular vesicles. Oncogene 2020;39:4477-90.
213. Treps L, Perret R, Edmond S, Ricard D, Gavard J. Glioblastoma stem-like cells secrete the pro-angiogenic VEGF-A factor in extracellular vesicles. J Extracell Vesicles 2017;6:1359479.
214. Sun X, Ma X, Wang J, et al. Glioma stem cells-derived exosomes promote the angiogenic ability of endothelial cells through miR-21/VEGF signal. Oncotarget 2017;8:36137-48.
215. Wang ZF, Liao F, Wu H, Dai J. Glioma stem cells-derived exosomal miR-26a promotes angiogenesis of microvessel endothelial cells in glioma. J Exp Clin Cancer Res 2019;38:201.
216. Liu S, Sun J, Lan Q. Glioblastoma microvesicles promote endothelial cell proliferation through Akt/beta-catenin pathway. Int J Clin Exp Pathol 2014;7:4857-66.
217. Al-Nedawi K, Meehan B, Micallef J, et al. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 2008;10:619-24.
218. Antonyak MA, Li B, Boroughs LK, et al. Cancer cell-derived microvesicles induce transformation by transferring tissue transglutaminase and fibronectin to recipient cells. Proc Natl Acad Sci U S A 2011;108:4852-7.
219. Lang HL, Hu GW, Chen Y, et al. Glioma cells promote angiogenesis through the release of exosomes containing long non-coding RNA POU3F3. Eur Rev Med Pharmacol Sci 2017;21:959-72.
220. Lang HL, Hu GW, Zhang B, et al. Glioma cells enhance angiogenesis and inhibit endothelial cell apoptosis through the release of exosomes that contain long non-coding RNA CCAT2. Oncol Rep 2017;38:785-98.
221. Bronisz A, Wang Y, Nowicki MO, et al. Extracellular vesicles modulate the glioblastoma microenvironment via a tumor suppression signaling network directed by miR-1. Cancer Res 2014;74:738-50.
222. Verhaak RG, Hoadley KA, Purdom E, et al. Cancer Genome Atlas Research Network. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010;17:98-110.
223. Suvà ML, Rheinbay E, Gillespie SM, et al. Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells. Cell 2014;157:580-94.
224. Berenguer J, Lagerweij T, Zhao XW, et al. Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8. J Extracell Vesicles 2018;7:1446660.
225. Lucero R, Zappulli V, Sammarco A, et al. Glioma-derived miRNA-containing extracellular vesicles induce angiogenesis by reprogramming brain endothelial cells. Cell Rep 2020;30:2065-74.e4.
226. Spinelli C, Montermini L, Meehan B, et al. Molecular subtypes and differentiation programmes of glioma stem cells as determinants of extracellular vesicle profiles and endothelial cell-stimulating activities. J Extracell Vesicles 2018;7:1490144.
227. Wei Z, Batagov AO, Schinelli S, et al. Coding and noncoding landscape of extracellular RNA released by human glioma stem cells. Nat Commun 2017;8:1145.
228. Hallal S, Mallawaaratchy DM, Wei H, et al. Extracellular Vesicles Released by Glioblastoma Cells Stimulate Normal Astrocytes to Acquire a Tumor-Supportive Phenotype Via p53 and MYC Signaling Pathways. Mol Neurobiol 2019;56:4566-81.
229. Colangelo NW, Azzam EI. Extracellular vesicles originating from glioblastoma cells increase metalloproteinase release by astrocytes: the role of CD147 (EMMPRIN) and ionizing radiation. Cell Commun Signal 2020;18:21.
230. Zeng A, Wei Z, Rabinovsky R, et al. Glioblastoma-Derived Extracellular Vesicles Facilitate Transformation of Astrocytes via Reprogramming Oncogenic Metabolism. iScience 2020;23:101420.
231. van der Vos KE, Abels ER, Zhang X, et al. Directly visualized glioblastoma-derived extracellular vesicles transfer RNA to microglia/macrophages in the brain. Neuro Oncol 2016;18:58-69.
232. de Vrij J, Maas SL, Kwappenberg KM, et al. Glioblastoma-derived extracellular vesicles modify the phenotype of monocytic cells. Int J Cancer 2015;137:1630-42.
233. Harshyne LA, Nasca BJ, Kenyon LC, Andrews DW, Hooper DC. Serum exosomes and cytokines promote a T-helper cell type 2 environment in the peripheral blood of glioblastoma patients. Neuro Oncol 2016;18:206-15.
234. Abels ER, Maas SLN, Nieland L, et al. Glioblastoma-Associated Microglia Reprogramming Is Mediated by Functional Transfer of Extracellular miR-21. Cell Rep 2019;28:3105-3119.e7.
235. Gabrusiewicz K, Li X, Wei J, et al. Glioblastoma stem cell-derived exosomes induce M2 macrophages and PD-L1 expression on human monocytes. Oncoimmunology 2018;7:e1412909.
236. Grimaldi A, Serpe C, Chece G, et al. Microglia-Derived Microvesicles Affect Microglia Phenotype in Glioma. Front Cell Neurosci 2019;13:41.
237. Ricklefs FL, Alayo Q, Krenzlin H, et al. Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles. Sci Adv 2018;4:eaar2766.
238. Munoz JL, Rodriguez-Cruz V, Ramkissoon SH, Ligon KL, Greco SJ, Rameshwar P. Temozolomide resistance in glioblastoma occurs by miRNA-9-targeted PTCH1, independent of sonic hedgehog level. Oncotarget 2015;6:1190-201.
239. Munoz JL, Bliss SA, Greco SJ, Ramkissoon SH, Ligon KL, Rameshwar P. Delivery of Functional Anti-miR-9 by Mesenchymal Stem Cell-derived Exosomes to Glioblastoma Multiforme Cells Conferred Chemosensitivity. Mol Ther Nucleic Acids 2013;2:e126.
240. Chuang HY, Su YK, Liu HW, et al. Preclinical Evidence of STAT3 Inhibitor Pacritinib Overcoming Temozolomide Resistance via Downregulating miR-21-Enriched Exosomes from M2 Glioblastoma-Associated Macrophages. J Clin Med 2019;8:959.
241. Figueroa JM, Skog J, Akers J, et al. Detection of wild-type EGFR amplification and EGFRvIII mutation in CSF-derived extracellular vesicles of glioblastoma patients. Neuro Oncol 2017;19:1494-502.
242. Akers JC, Ramakrishnan V, Kim R, et al. MiR-21 in the extracellular vesicles (EVs) of cerebrospinal fluid (CSF): a platform for glioblastoma biomarker development. PLoS One 2013;8:e78115.
