This table summarizes the cell-type-specific characteristics and functions of EVs produced by different CNS cell types, highlighting their diverse roles in neural communication and homeostasis. BBB: blood-brain barrier; CNS: central nervous system; EV: extracellular vesicle; GAPDH: glyceraldehyde-3-phosphate dehydrogenase.
Declarations
Author contributions
MAM: Writing—original draft, Writing—review & editing, Visualization. MMH: Conceptualization, Writing—original draft, Writing—review & editing, Visualization. Both authors read and approved the submitted version.
Conflicts of interest
The authors declare that they have no conflicts of interest.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.
References
Ding C, Wu Y, Chen X, Chen Y, Wu Z, Lin Z, et al. Global, regional, and national burden and attributable risk factors of neurological disorders: The Global Burden of Disease study 1990–2019.Front Public Health. 2022;10:952161. [DOI] [PubMed] [PMC]
Nehra A. Role of neuropsychology in continuum of health care in neurological conditions.Neurol India. 2019;67:404–9. [DOI] [PubMed]
GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016.Lancet Neurol. 2019;18:459–80. [DOI] [PubMed] [PMC]
Savelieff MG, Nam G, Kang J, Lee HJ, Lee M, Lim MH. Development of Multifunctional Molecules as Potential Therapeutic Candidates for Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis in the Last Decade.Chem Rev. 2019;119:1221–322. [DOI] [PubMed]
Quek C, Hill AF. The role of extracellular vesicles in neurodegenerative diseases.Biochem Biophys Res Commun. 2017;483:1178–86. [DOI] [PubMed]
Capobianco DL, Simone L, Svelto M, Pisani F. Intercellular crosstalk mediated by tunneling nanotubes between central nervous system cells. What we need to advance.Front Physiol. 2023;14:1214210. [DOI] [PubMed] [PMC]
Vainchtein ID, Molofsky AV. Astrocytes and Microglia: In Sickness and in Health.Trends Neurosci. 2020;43:144–54. [DOI] [PubMed] [PMC]
Verkhratsky A, Nedergaard M. Physiology of Astroglia.Physiol Rev. 2018;98:239–389. [DOI] [PubMed] [PMC]
Filannino FM, Panaro MA, Benameur T, Pizzolorusso I, Porro C. Extracellular Vesicles in the Central Nervous System: A Novel Mechanism of Neuronal Cell Communication.Int J Mol Sci. 2024;25:1629. [DOI] [PubMed] [PMC]
Mahjoum S, Rufino-Ramos D, Pereira de Almeida L, Broekman MLD, Breakefield XO, van Solinge TS. Living Proof of Activity of Extracellular Vesicles in the Central Nervous System.Int J Mol Sci. 2021;22:7294. [DOI] [PubMed] [PMC]
Ramirez SH, Andrews AM, Paul D, Pachter JS. Extracellular vesicles: mediators and biomarkers of pathology along CNS barriers.Fluids Barriers CNS. 2018;15:19. [DOI] [PubMed] [PMC]
Zappulli V, Friis KP, Fitzpatrick Z, Maguire CA, Breakefield XO. Extracellular vesicles and intercellular communication within the nervous system.J Clin Invest. 2016;126:1198–207. [DOI] [PubMed] [PMC]
Mimi MA, Hasan MM, Takanashi Y, Waliullah ASM, Mamun MA, Chi Z, et al. UBL3 overexpression enhances EV-mediated Achilles protein secretion in conditioned media of MDA-MB-231 cells.Biochem Biophys Res Commun. 2024;738:150559. [DOI] [PubMed]
Zhang L, Parot J, Hackley VA, Turko IV. Quantitative Proteomic Analysis of Biogenesis-Based Classification for Extracellular Vesicles.Proteomes. 2020;8:33. [DOI] [PubMed] [PMC]
van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles.Nat Rev Mol Cell Biol. 2018;19:213–28. [DOI] [PubMed]
Thompson AG, Gray E, Heman-Ackah SM, Mäger I, Talbot K, Andaloussi SE, et al. Extracellular vesicles in neurodegenerative disease—pathogenesis to biomarkers.Nat Rev Neurol. 2016;12:346–57. [DOI] [PubMed]
Dixson AC, Dawson TR, Di Vizio D, Weaver AM. Context-specific regulation of extracellular vesicle biogenesis and cargo selection.Nat Rev Mol Cell Biol. 2023;24:454–76. [DOI] [PubMed] [PMC]
Anand S, Samuel M, Kumar S, Mathivanan S. Ticket to a bubble ride: Cargo sorting into exosomes and extracellular vesicles.Biochim Biophys Acta Proteins Proteom. 2019;1867:140203. [DOI] [PubMed]
Downes BP, Saracco SA, Lee SS, Crowell DN, Vierstra RD. MUBs, a family of ubiquitin-fold proteins that are plasma membrane-anchored by prenylation.J Biol Chem. 2006;281:27145–57. [DOI] [PubMed]
Takanashi Y, Kahyo T, Kamamoto S, Zhang H, Chen B, Ping Y, et al. Ubiquitin-like 3 as a new protein-sorting factor for small extracellular vesicles.Cell Struct Funct. 2022;47:1–18. [DOI] [PubMed] [PMC]
Cabrera-Pastor A. Extracellular Vesicles as Mediators of Neuroinflammation in Intercellular and Inter-Organ Crosstalk.Int J Mol Sci. 2024;25:7041. [DOI] [PubMed] [PMC]
Wiersema AF, Rennenberg A, Smith G, Varderidou-Minasian S, Pasterkamp RJ. Shared and distinct changes in the molecular cargo of extracellular vesicles in different neurodegenerative diseases.Cell Mol Life Sci. 2024;81:479. [DOI] [PubMed] [PMC]
Hill AF. Extracellular Vesicles and Neurodegenerative Diseases.J Neurosci. 2019;39:9269–73. [DOI] [PubMed] [PMC]
Vandendriessche C, Bruggeman A, Van Cauwenberghe C, Vandenbroucke RE. Extracellular Vesicles in Alzheimer’s and Parkinson’s Disease: Small Entities with Large Consequences.Cells. 2020;9:2485. [DOI] [PubMed] [PMC]
Manna I, De Benedittis S, Porro D. Extracellular Vesicles in Multiple Sclerosis: Their Significance in the Development and Possible Applications as Therapeutic Agents and Biomarkers.Genes (Basel). 2024;15:772. [DOI] [PubMed] [PMC]
Pistono C, Osera C, Cuccia M, Bergamaschi R. Roles of Extracellular Vesicles in Multiple Sclerosis: From Pathogenesis to Potential Tools as Biomarkers and Therapeutics.Scler. 2023;1:91–112. [DOI]
Malaguarnera M, Cabrera-Pastor A. Emerging Role of Extracellular Vesicles as Biomarkers in Neurodegenerative Diseases and Their Clinical and Therapeutic Potential in Central Nervous System Pathologies.Int J Mol Sci. 2024;25:10068. [DOI] [PubMed] [PMC]
Isik M, Sari HK, Caglayan MG, Yilmaz R, Derkus B. Whispers in the Brain: Extracellular Vesicles in Neuropathology and the Diagnostic Alchemy of Neurological Diseases.Eur J Neurosci. 2025;61:e70090. [DOI] [PubMed]
Yadav A, Xuan Y, Sen CK, Ghatak S. Standardized Reporting of Research on Exosomes to Ensure Rigor and Reproducibility.Adv Wound Care (New Rochelle). 2024;13:584–99. [DOI] [PubMed] [PMC]
Gandham S, Su X, Wood J, Nocera AL, Alli SC, Milane L, et al. Technologies and Standardization in Research on Extracellular Vesicles.Trends Biotechnol. 2020;38:1066–98. [DOI] [PubMed] [PMC]
Yan J, Kahyo T, Zhang H, Ping Y, Zhang C, Jiang S, et al. Alpha-Synuclein Interaction with UBL3 Is Upregulated by Microsomal Glutathione S-Transferase 3, Leading to Increased Extracellular Transport of the Alpha-Synuclein under Oxidative Stress.Int J Mol Sci. 2024;25:7353. [DOI] [PubMed] [PMC]
Oyama S, Zhang H, Ferdous R, Tomochika Y, Chen B, Jiang S, et al. UBL3 Interacts with PolyQ-Expanded Huntingtin Fragments and Modifies Their Intracellular Sorting.Neurol Int. 2024;16:1175–88. [DOI] [PubMed] [PMC]
Zhang H, Chen B, Waliullah ASM, Aramaki S, Ping Y, Takanashi Y, et al. A New Potential Therapeutic Target for Cancer in Ubiquitin-Like Proteins-UBL3.Int J Mol Sci. 2023;24:1231. [DOI] [PubMed] [PMC]
Pistono C, Bister N, Stanová I, Malm T. Glia-Derived Extracellular Vesicles: Role in Central Nervous System Communication in Health and Disease.Front Cell Dev Biol. 2021;8:623771. [DOI] [PubMed] [PMC]
Yang J, Cao LL, Wang XP, Guo W, Guo RB, Sun YQ, et al. Neuronal extracellular vesicle derived miR-98 prevents salvageable neurons from microglial phagocytosis in acute ischemic stroke.Cell Death Dis. 2021;12:23. [DOI] [PubMed] [PMC]
Blanchette CR, Rodal AA. Mechanisms for biogenesis and release of neuronal extracellular vesicles.Curr Opin Neurobiol. 2020;63:104–10. [DOI] [PubMed] [PMC]
Frühbeis C, Kuo-Elsner WP, Müller C, Barth K, Peris L, Tenzer S, et al. Oligodendrocytes support axonal transport and maintenance via exosome secretion.PLoS Biol. 2020;18:e3000621. [DOI] [PubMed] [PMC]
Fröhlich D, Kuo WP, Frühbeis C, Sun JJ, Zehendner CM, Luhmann HJ, et al. Multifaceted effects of oligodendroglial exosomes on neurons: impact on neuronal firing rate, signal transduction and gene regulation.Philos Trans R Soc Lond B Biol Sci. 2014;369:20130510. [DOI] [PubMed] [PMC]
Pascua-Maestro R, González E, Lillo C, Ganfornina MD, Falcón-Pérez JM, Sanchez D. Extracellular Vesicles Secreted by Astroglial Cells Transport Apolipoprotein D to Neurons and Mediate Neuronal Survival Upon Oxidative Stress.Front Cell Neurosci. 2019;12:526. [DOI] [PubMed] [PMC]
Ceccarelli L, Giacomelli C, Marchetti L, Martini C. Microglia extracellular vesicles: focus on molecular composition and biological function.Biochem Soc Trans. 2021;49:1779–90. [DOI] [PubMed]
Santiago JV, Natu A, Ramelow CC, Rayaprolu S, Xiao H, Kumar V, et al. Identification of State-Specific Proteomic and Transcriptomic Signatures of Microglia-Derived Extracellular Vesicles.Mol Cell Proteomics. 2023;22:100678. [DOI] [PubMed] [PMC]
Lombardi M, Gabrielli M, Adinolfi E, Verderio C. Role of ATP in Extracellular Vesicle Biogenesis and Dynamics.Front Pharmacol. 2021;12:654023. [DOI] [PubMed] [PMC]
Juan T, Fürthauer M. Biogenesis and function of ESCRT-dependent extracellular vesicles.Semin Cell Dev Biol. 2018;74:66–77. [DOI] [PubMed]
Krämer-Albers E. Extracellular vesicles in the oligodendrocyte microenvironment.Neurosci Lett. 2020;725:134915. [DOI] [PubMed]
Hasan MM, Mimi MA, Mamun MA, Islam A, Waliullah ASM, Nabi MM, et al. Mass Spectrometry Imaging for Glycome in the Brain.Front Neuroanat. 2021;15:711955. [DOI] [PubMed] [PMC]
Hasan MM, Mimi MA, Kikushima K, Kahyo T, Setou M. Mass spectrometry imaging for glycosphingolipids. In: Nishihara S, Angata K, Aoki-Kinoshita KF, Hirabayashi J, editors. Glycoscience Protocols (GlycoPODv2) [Internet]. Saitama (JP): Japan Consortium for Glycobiology and Glycotechnology; 2021. [PubMed]
Fyfe J, Casari I, Manfredi M, Falasca M. Role of lipid signalling in extracellular vesicles-mediated cell-to-cell communication.Cytokine Growth Factor Rev. 2023;73:20–6. [DOI] [PubMed]
O’Brien K, Breyne K, Ughetto S, Laurent LC, Breakefield XO. RNA delivery by extracellular vesicles in mammalian cells and its applications.Nat Rev Mol Cell Biol. 2020;21:585–606. [DOI] [PubMed] [PMC]
Lai Z, Ye T, Zhang M, Mu Y. Exosomes as Vehicles for Noncoding RNA in Modulating Inflammation: A Promising Regulatory Approach for Ischemic Stroke and Myocardial Infarction.J Inflamm Res. 2024;17:7485–501. [DOI] [PubMed] [PMC]
Alexander M, O’Connell R. Exosomal MiRNAs Regulate Inflammatory Responses (IRM11P.624).J Immunol. 2015;194:132.3. [DOI]
Okeoma CM, Naushad W, Okeoma BC, Gartner C, Santos-Ortega Y, Vary C, et al. Lipidomic and proteomic insights from extracellular vesicles in the postmortem dorsolateral prefrontal cortex reveal substance use disorder-induced brain changes.Transl Psychiatry. 2025;15:284. [DOI] [PubMed] [PMC]
Wubbolts R, Leckie RS, Veenhuizen PT, Schwarzmann G, Möbius W, Hoernschemeyer J, et al. Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation.J Biol Chem. 2003;278:10963–72. [DOI] [PubMed]
Lee YJ, Shin KJ, Chae YC. Regulation of cargo selection in exosome biogenesis and its biomedical applications in cancer.Exp Mol Med. 2024;56:877–89. [DOI] [PubMed] [PMC]
Leidal AM, Debnath J. Unraveling the mechanisms that specify molecules for secretion in extracellular vesicles.Methods. 2020;177:15–26. [DOI] [PubMed] [PMC]
Li SP, Lin ZX, Jiang XY, Yu XY. Exosomal cargo-loading and synthetic exosome-mimics as potential therapeutic tools.Acta Pharmacol Sin. 2018;39:542–51. [DOI] [PubMed] [PMC]
Atukorala I, Mathivanan S. The Role of Post-Translational Modifications in Targeting Protein Cargo to Extracellular Vesicles.Subcell Biochem. 2021;97:45–60. [DOI] [PubMed]
Waury K, Gogishvili D, Nieuwland R, Chatterjee M, Teunissen CE, Abeln S. Proteome encoded determinants of protein sorting into extracellular vesicles.J Extracell Biol. 2024;3:e120. [DOI] [PubMed] [PMC]
Villarroya-Beltri C, Gutiérrez-Vázquez C, Sánchez-Cabo F, Pérez-Hernández D, Vázquez J, Martin-Cofreces N, et al. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs.Nat Commun. 2013;4:2980. [DOI] [PubMed] [PMC]
Ageta H, Ageta-Ishihara N, Hitachi K, Karayel O, Onouchi T, Yamaguchi H, et al. UBL3 modification influences protein sorting to small extracellular vesicles.Nat Commun. 2018;9:3936. [DOI] [PubMed] [PMC]
Mulcahy LA, Pink RC, Carter DRF. Routes and mechanisms of extracellular vesicle uptake.J Extracell Vesicles. 2014;3:24641. [DOI] [PubMed] [PMC]
Horibe S, Tanahashi T, Kawauchi S, Murakami Y, Rikitake Y. Mechanism of recipient cell-dependent differences in exosome uptake.BMC Cancer. 2018;18:47. [DOI] [PubMed] [PMC]
Atai NA, Balaj L, van Veen H, Breakefield XO, Jarzyna PA, Van Noorden CJ, et al. Heparin blocks transfer of extracellular vesicles between donor and recipient cells.J Neurooncol. 2013;115:343–51. [DOI] [PubMed] [PMC]
Tian T, Zhu YL, Zhou YY, Liang GF, Wang YY, Hu FH, et al. Exosome uptake through clathrin-mediated endocytosis and macropinocytosis and mediating miR-21 delivery.J Biol Chem. 2014;289:22258–67. [DOI] [PubMed] [PMC]
Fitzner D, Schnaars M, van Rossum D, Krishnamoorthy G, Dibaj P, Bakhti M, et al. Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis.J Cell Sci. 2011;124:447–58. [DOI] [PubMed]
Kunadt M, Eckermann K, Stuendl A, Gong J, Russo B, Strauss K, et al. Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation.Acta Neuropathol. 2015;129:695–713. [DOI] [PubMed] [PMC]
Wu L, Gao C. Comprehensive Overview the Role of Glycosylation of Extracellular Vesicles in Cancers.ACS Omega. 2023;8:47380–92. [DOI] [PubMed] [PMC]
Dowil RT, Lu X, Saracco SA, Vierstra RD, Downes BP. Arabidopsis membrane-anchored ubiquitin-fold (MUB) proteins localize a specific subset of ubiquitin-conjugating (E2) enzymes to the plasma membrane.J Biol Chem. 2011;286:14913–21. [DOI] [PubMed] [PMC]
Lu X, Malley KR, Brenner CC, Koroleva O, Korolev S, Downes BP. A MUB E2 structure reveals E1 selectivity between cognate ubiquitin E2s in eukaryotes.Nat Commun. 2016;7:12580. [DOI] [PubMed] [PMC]
Vierstra RD. The expanding universe of ubiquitin and ubiquitin-like modifiers.Plant Physiol. 2012;160:2–14. [DOI] [PubMed] [PMC]
Ageta H, Tsuchida K. Post-translational modification and protein sorting to small extracellular vesicles including exosomes by ubiquitin and UBLs.Cell Mol Life Sci. 2019;76:4829–48. [DOI] [PubMed] [PMC]
Mimi MA, Hasan MM. Extracellular Vesicles as Mediators of Intercellular Communication: Implications for Drug Discovery and Targeted Therapies.Future Pharmacol. 2025;5:48. [DOI]
Maihemuti M, Mimi MA, Sohag SM, Hasan MM. Single-Cell Transcriptomics in Spinal Cord Studies: Progress and Perspectives.BioChem. 2025;5:16. [DOI]
Li X, Huang Z, Shu M, Hu G, Yi W, Duan Y, et al. Bone Mesenchymal Stromal Cell-Derived Extracellular Vesicles Protect Articular Cartilage Through Regulating tRF-Gln-TTG-019/UBL3.Mediators Inflamm. 2025;2025:2705953. [DOI] [PubMed] [PMC]
Terada Y, Obara K, Yoshioka Y, Ochiya T, Bito H, Tsuchida K, et al. Intracellular dynamics of ubiquitin-like 3 visualized using an inducible fluorescent timer expression system.Biol Open. 2024;13:bio060345. [DOI] [PubMed] [PMC]
Ageta H, Nishioka T, Yamaguchi H, Tsuchida K, Ageta-Ishihara N. Comprehensive identification of ubiquitin-like 3 (UBL3)-interacting proteins in the mouse brain.Mol Brain. 2024;17:57. [DOI] [PubMed] [PMC]
Quan VL, Zhang B, Mohan LS, Shi K, Isales MC, Panah E, et al. Activating Structural Alterations in MAPK Genes Are Distinct Genetic Drivers in a Unique Subgroup Of Spitzoid Neoplasms.Am J Surg Pathol. 2019;43:538–48. [DOI] [PubMed]
Houlier A, Pissaloux D, Masse I, Tirode F, Karanian M, Pincus LB, et al. Melanocytic tumors with MAP3K8 fusions: report of 33 cases with morphological-genetic correlations.Mod Pathol. 2020;33:846–57. [DOI] [PubMed]
Lee JY, Kim J, Kim SW, Park SK, Ahn SH, Lee MH, et al. BRCA1/2-negative, high-risk breast cancers (BRCAX) for Asian women: genetic susceptibility loci and their potential impacts.Sci Rep. 2018;8:15263. [DOI] [PubMed] [PMC]
Sohag SM, Toma SN, Imon MAI, Maihemuti M, Ahmed F, Mimi MA, et al. Tumor Microenvironment: An Emerging Landscape for Lung Cancer Therapy.Future Pharmacol. 2025;5:34. [DOI]
Krokidis MG, Pucha KA, Mustapic M, Exarchos TP, Vlamos P, Kapogiannis D. Lipidomic Analysis of Plasma Extracellular Vesicles Derived from Alzheimer’s Disease Patients.Cells. 2024;13:702. [DOI] [PubMed] [PMC]
ten Broeke T, Wubbolts R, Stoorvogel W. MHC class II antigen presentation by dendritic cells regulated through endosomal sorting.Cold Spring Harb Perspect Biol. 2013;5:a016873. [DOI] [PubMed] [PMC]
Groot M, Lee H. Sorting Mechanisms for MicroRNAs into Extracellular Vesicles and Their Associated Diseases.Cells. 2020;9:1044. [DOI] [PubMed] [PMC]
Rajendran L, Bali J, Barr MM, Court FA, Krämer-Albers EM, Picou F, et al. Emerging roles of extracellular vesicles in the nervous system.J Neurosci. 2014;34:15482–9. [DOI] [PubMed] [PMC]
Chen B, Hasan MM, Zhang H, Zhai Q, Waliullah ASM, Ping Y, et al. UBL3 Interacts with Alpha-Synuclein in Cells and the Interaction Is Downregulated by the EGFR Pathway Inhibitor Osimertinib.Biomedicines. 2023;11:1685. [DOI] [PubMed] [PMC]
Liu X, Hebron M, Shi W, Lonskaya I, Moussa CE. Ubiquitin specific protease-13 independently regulates parkin ubiquitination and alpha-synuclein clearance in alpha-synucleinopathies.Hum Mol Genet. 2019;28:548–60. [DOI] [PubMed]
Pérez M, Avila J, Hernández F. Propagation of Tau via Extracellular Vesicles.Front Neurosci. 2019;13:698. [DOI] [PubMed] [PMC]
Aulston B, Liu Q, Mante M, Florio J, Rissman RA, Yuan SH. Extracellular Vesicles Isolated from Familial Alzheimer’s Disease Neuronal Cultures Induce Aberrant Tau Phosphorylation in the Wild-Type Mouse Brain.J Alzheimers Dis. 2019;72:575–85. [DOI] [PubMed] [PMC]
Fowler SL, Behr TS, Turkes E, O’Brien DP, Cauhy PM, Rawlinson I, et al. Tau filaments are tethered within brain extracellular vesicles in Alzheimer’s disease.Nat Neurosci. 2025;28:40–8. [DOI] [PubMed] [PMC]
Gupta A, Pulliam L. Exosomes as mediators of neuroinflammation.J Neuroinflammation. 2014;11:68. [DOI] [PubMed] [PMC]
Shippey LE, Campbell SG, Hill AF, Smith DP. Propagation of Parkinson’s disease by extracellular vesicle production and secretion.Biochem Soc Trans. 2022;50:1303–14. [DOI] [PubMed] [PMC]
Volarevic A, Harrell CR, Arsenijevic A, Djonov V, Volarevic V. Therapeutic Potential of Mesenchymal Stem Cell-Derived Extracellular Vesicles in the Treatment of Parkinson's Disease.Cells. 2025;14:600. [DOI] [PubMed] [PMC]
Vilaça-Faria H, Salgado AJ, Teixeira FG. Mesenchymal Stem Cells-derived Exosomes: A New Possible Therapeutic Strategy for Parkinson’s Disease?Cells. 2019;8:118. [DOI] [PubMed] [PMC]
Dellar ER, Nikel L, Fowler S, Vahsen BF, Dafinca R, Feneberg E, et al. Extracellular vesicles in TDP-43 proteinopathies: pathogenesis and biomarker potential.Mol Neurodegener. 2025;20:68. [DOI] [PubMed] [PMC]
Sproviero D, La Salvia S, Giannini M, Crippa V, Gagliardi S, Bernuzzi S, et al. Pathological Proteins Are Transported by Extracellular Vesicles of Sporadic Amyotrophic Lateral Sclerosis Patients.Front Neurosci. 2018;12:487. [DOI] [PubMed] [PMC]
Codron P, Millecamps S, Corcia P. EVolution in ALS diagnosis: molecular markers in extracellular vesicles.Trends Mol Med. 2024;30:1097–9. [DOI] [PubMed]
Zamboni S, D’Ambrosio A, Margutti P. Extracellular vesicles as contributors in the pathogenesis of multiple sclerosis.Mult Scler Relat Disord. 2023;71:104554. [DOI] [PubMed]
Dolcetti E, Bruno A, Guadalupi L, Rizzo FR, Musella A, Gentile A, et al. Emerging Role of Extracellular Vesicles in the Pathophysiology of Multiple Sclerosis.Int J Mol Sci. 2020;21:7336. [DOI] [PubMed] [PMC]
Wang X, Li A, Fan H, Li Y, Yang N, Tang Y. Astrocyte-Derived Extracellular Vesicles for Ischemic Stroke: Therapeutic Potential and Prospective.Aging Dis. 2024;15:1227–54. [DOI] [PubMed] [PMC]
Reymond S, Vujić T, Sanchez JC. Neurovascular Unit-Derived Extracellular Vesicles: From Their Physiopathological Roles to Their Clinical Applications in Acute Brain Injuries.Biomedicines. 2022;10:2147. [DOI] [PubMed] [PMC]
Upadhya D, Shetty AK. Promise of extracellular vesicles for diagnosis and treatment of epilepsy.Epilepsy Behav. 2021;121:106499. [DOI] [PubMed] [PMC]
Tallon C, Hollinger KR, Pal A, Bell BJ, Rais R, Tsukamoto T, et al. Nipping disease in the bud: nSMase2 inhibitors as therapeutics in extracellular vesicle-mediated diseases.Drug Discov Today. 2021;26:1656–68. [DOI] [PubMed] [PMC]
Hao Y, Song H, Zhou Z, Chen X, Li H, Zhang Y, et al. Promotion or inhibition of extracellular vesicle release: Emerging therapeutic opportunities.J Control Release. 2021;340:136–48. [DOI] [PubMed]
Huang M, Tallon C, Bell BJ, Kapogiannis D, Haughey NJ, Rais R, et al. Inhibition of EV Biogenesis Reduces Tau Propagation in Alzheimer’s Disease Mouse Models.Alzheimers Dement. 2023;19:e078341. [DOI]
Welton JL, Loveless S, Stone T, von Ruhland C, Robertson NP, Clayton A. Cerebrospinal fluid extracellular vesicle enrichment for protein biomarker discovery in neurological disease; multiple sclerosis.J Extracell Vesicles. 2017;6:1369805. [DOI] [PubMed] [PMC]
Anandan S, Maciak K, Breinbauer R, Mostafavi S, Kvistad CE, Torkildsen O, et al. Brain-derived blood biomarkers in multiple sclerosis-current trends and beyond.Front Immunol. 2025;16:1569503. [DOI] [PubMed] [PMC]
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. [DOI] [PubMed] [PMC]
Li C, Wang C, Zhang Y, Alsrouji OK, Chebl AB, Ding G, et al. Cerebral endothelial cell-derived small extracellular vesicles enhance neurovascular function and neurological recovery in rat acute ischemic stroke models of mechanical thrombectomy and embolic stroke treatment with tPA.J Cereb Blood Flow Metab. 2021;41:2090–104. [DOI] [PubMed] [PMC]
Fan C, Li Y, Lan T, Wang W, Long Y, Yu SY. Microglia secrete miR-146a-5p-containing exosomes to regulate neurogenesis in depression.Mol Ther. 2022;30:1300–14. [DOI] [PubMed] [PMC]
Wei ZX, Xie GJ, Mao X, Zou XP, Liao YJ, Liu QS, et al. Exosomes from patients with major depression cause depressive-like behaviors in mice with involvement of miR-139-5p-regulated neurogenesis.Neuropsychopharmacology. 2020;45:1050–8. [DOI] [PubMed] [PMC]
Antoniou A, Auderset L, Kaurani L, Sebastian E, Zeng Y, Allahham M, et al. Neuronal extracellular vesicles and associated microRNAs induce circuit connectivity downstream BDNF.Cell Rep. 2023;42:112063. [DOI] [PubMed]
Yu X, Bai Y, Han B, Ju M, Tang T, Shen L, et al. Extracellular vesicle-mediated delivery of circDYM alleviates CUS-induced depressive-like behaviours.J Extracell Vesicles. 2022;11:e12185. [DOI] [PubMed] [PMC]
Goetzl EJ, Wolkowitz OM, Srihari VH, Reus VI, Goetzl L, Kapogiannis D, et al. Abnormal levels of mitochondrial proteins in plasma neuronal extracellular vesicles in major depressive disorder.Mol Psychiatry. 2021;26:7355–62. [DOI] [PubMed] [PMC]
Han B, Zhou S, Zhang Y, Chen S, Xi W, Liu C, et al. Integrating spatial and single-cell transcriptomics to characterize the molecular and cellular architecture of the ischemic mouse brain.Sci Transl Med. 2024;16:eadg1323. [DOI] [PubMed]
Huang JH, Xu Y, Yin XM, Lin FY. Exosomes Derived from miR-126-modified MSCs Promote Angiogenesis and Neurogenesis and Attenuate Apoptosis after Spinal Cord Injury in Rats.Neuroscience. 2020;424:133–45. [DOI] [PubMed]
Lassen TR, Just J, Hjortbak MV, Jespersen NR, Stenz KT, Gu T, et al. Cardioprotection by remote ischemic conditioning is transferable by plasma and mediated by extracellular vesicles.Basic Res Cardiol. 2021;116:16. [DOI] [PubMed]
Zhang R, Mao W, Niu L, Bao W, Wang Y, Wang Y, et al. NSC-derived exosomes enhance therapeutic effects of NSC transplantation on cerebral ischemia in mice.Elife. 2023;12:e84493. [DOI] [PubMed] [PMC]
Liang X, Miao Y, Tong X, Chen J, Liu H, He Z, et al. Dental pulp mesenchymal stem cell-derived exosomes inhibit neuroinflammation and microglial pyroptosis in subarachnoid hemorrhage via the miRNA-197-3p/FOXO3 axis.J Nanobiotechnology. 2024;22:426. [DOI] [PubMed] [PMC]
Wang P, Dong S, Liu F, Liu A, Wang Z. MicroRNA-140-5p shuttled by microglia-derived extracellular vesicles attenuates subarachnoid hemorrhage-induced microglia activation and inflammatory response via MMD downregulation.Exp Neurol. 2023;359:114265. [DOI] [PubMed]
Sanchez Trivino CA, Spelat R, Spada F, D’Angelo C, Manini I, Rolle IG, et al. Exosomal TNF-α mediates voltage-gated Na+ channel 1.6 overexpression and contributes to brain tumor-induced neuronal hyperexcitability.J Clin Invest. 2024;134:e166271. [DOI] [PubMed] [PMC]
Cukovic D, Bagla S, Ukasik D, Stemmer PM, Jena BP, Naik AR, et al. Exosomes in Epilepsy of Tuberous Sclerosis Complex: Carriers of Pro-Inflammatory MicroRNAs.Noncoding RNA. 2021;7:40. [DOI] [PubMed] [PMC]
Ma M, Cheng Y, Hou X, Li Z, Wang M, Ma B, et al. Serum biomarkers in patients with drug-resistant epilepsy: a proteomics-based analysis.Front Neurol. 2024;15:1383023. [DOI] [PubMed] [PMC]
Yang Z, Shi J, Xie J, Wang Y, Sun J, Liu T, et al. Large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation.Nat Biomed Eng. 2020;4:69–83. [DOI] [PubMed] [PMC]
Kim J, Zhu Y, Chen S, Wang D, Zhang S, Xia J, et al. Anti-glioma effect of ginseng-derived exosomes-like nanoparticles by active blood-brain-barrier penetration and tumor microenvironment modulation.J Nanobiotechnology. 2023;21:253. [DOI] [PubMed] [PMC]
Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers.Nat Cell Biol. 2008;10:1470–6. [DOI] [PubMed] [PMC]
Guo X, Qiu W, Wang C, Qi Y, Li B, Wang S, et al. Neuronal Activity Promotes Glioma Progression by Inducing Proneural-to-Mesenchymal Transition in Glioma Stem Cells.Cancer Res. 2024;84:372–87. [DOI] [PubMed]
Tominaga N, Kosaka N, Ono M, Katsuda T, Yoshioka Y, Tamura K, et al. Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier.Nat Commun. 2015;6:6716. [DOI] [PubMed] [PMC]
Gao X, Zhang Z, Mashimo T, Shen B, Nyagilo J, Wang H, et al. Gliomas Interact with Non-glioma Brain Cells via Extracellular Vesicles.Cell Rep. 2020;30:2489–500.e5. [DOI] [PubMed]
Gyuris A, Navarrete-Perea J, Jo A, Cristea S, Zhou S, Fraser K, et al. Physical and Molecular Landscapes of Mouse Glioma Extracellular Vesicles Define Heterogeneity.Cell Rep. 2019;27:3972–87.e6. [DOI] [PubMed] [PMC]
Thakur A, Qiu G, Xu C, Han X, Yang T, Ng SP, et al. Label-free sensing of exosomal MCT1 and CD147 for tracking metabolic reprogramming and malignant progression in glioma.Sci Adv. 2020;6:eaaz6119. [DOI] [PubMed] [PMC]
Rooj AK, Ricklefs F, Mineo M, Nakano I, Chiocca EA, Bronisz A, et al. MicroRNA-Mediated Dynamic Bidirectional Shift between the Subclasses of Glioblastoma Stem-like Cells.Cell Rep. 2017;19:2026–32. [DOI] [PubMed] [PMC]
Wei Z, Batagov AO, Schinelli S, Wang J, Wang Y, El Fatimy R, et al. Coding and noncoding landscape of extracellular RNA released by human glioma stem cells.Nat Commun. 2017;8:1145. [DOI] [PubMed] [PMC]
Song Y, Shi R, Liu Y, Cui F, Han L, Wang C, et al. M2 Microglia Extracellular Vesicle miR-124 Regulates Neural Stem Cell Differentiation in Ischemic Stroke via AAK1/NOTCH.Stroke. 2023;54:2629–39. [DOI] [PubMed]
Sheng B, Lai N, Tao T, Chen X, Gao S, Zhu Q, et al. Diagnosis potential of subarachnoid hemorrhage using miRNA signatures isolated from plasma-derived extracellular vesicles.Front Pharmacol. 2023;14:1090389. [DOI] [PubMed] [PMC]
Zhou X, Xie F, Wang L, Zhang L, Zhang S, Fang M, et al. The function and clinical application of extracellular vesicles in innate immune regulation.Cell Mol Immunol. 2020;17:323–34. [DOI] [PubMed] [PMC]
Taha HB. Alzheimer’s Disease and Related Dementias Diagnosis: A Biomarkers Meta-Analysis of General and CNS Extracellular Vesicles.npj Dement. 2025;1:1–35. [DOI]
van der Pol E, Böing AN, Harrison P, Sturk A, Nieuwland R. Classification, functions, and clinical relevance of extracellular vesicles.Pharmacol Rev. 2012;64:676–705. [DOI] [PubMed]
Xu X, Iqbal Z, Xu L, Wen C, Duan L, Xia J, et al. Brain-derived extracellular vesicles: Potential diagnostic biomarkers for central nervous system diseases.Psychiatry Clin Neurosci. 2024;78:83–96. [DOI] [PubMed]
Shirmast P, Shahri MA, Brent A, Idris A, McMillan NAJ. Delivering therapeutic RNA into the brain using extracellular vesicles.Mol Ther Nucleic Acids. 2024;35:102373. [DOI] [PubMed] [PMC]
Chen T, Chen D, Su W, Liang J, Liu X, Cai M. Extracellular vesicles as vital players in drug delivery: a focus on clinical disease treatment.Front Bioeng Biotechnol. 2025;13:1600227. [DOI] [PubMed] [PMC]
Li P, Kaslan M, Lee SH, Yao J, Gao Z. Progress in Exosome Isolation Techniques.Theranostics. 2017;7:789–804. [DOI] [PubMed] [PMC]
Liang X, Gupta D, Xie J, Van Wonterghem E, Van Hoecke L, Hean J, et al. Engineering of extracellular vesicles for efficient intracellular delivery of multimodal therapeutics including genome editors.Nat Commun. 2025;16:4028. [DOI] [PubMed] [PMC]
Rong Y, Wang Z, Tang P, Wang J, Ji C, Chang J, et al. Engineered extracellular vesicles for delivery of siRNA promoting targeted repair of traumatic spinal cord injury.Bioact Mater. 2022;23:328–42. [DOI] [PubMed] [PMC]
Kang JY, Mun D, Chun Y, Park DS, Kim H, Yun N, et al. Engineered small extracellular vesicle-mediated NOX4 siRNA delivery for targeted therapy of cardiac hypertrophy.J Extracell Vesicles. 2023;12:e12371. [DOI] [PubMed] [PMC]
Yuan Y, Sun J, You T, Shen W, Xu W, Dong Q, et al. Extracellular Vesicle-Based Therapeutics in Neurological Disorders.Pharmaceutics. 2022;14:2652. [DOI] [PubMed] [PMC]
Orefice NS. Development of New Strategies Using Extracellular Vesicles Loaded with Exogenous Nucleic Acid.Pharmaceutics. 2020;12:705. [DOI] [PubMed] [PMC]
Wang J, Bonacquisti EE, Brown AD, Nguyen J. Boosting the Biogenesis and Secretion of Mesenchymal Stem Cell-Derived Exosomes.Cells. 2020;9:660. [DOI] [PubMed] [PMC]
Corso G, Mäger I, Lee Y, Görgens A, Bultema J, Giebel B, et al. Reproducible and scalable purification of extracellular vesicles using combined bind-elute and size exclusion chromatography.Sci Rep. 2017;7:11561. [DOI] [PubMed] [PMC]
Maguire CA, Balaj L, Sivaraman S, Crommentuijn MH, Ericsson M, Mincheva-Nilsson L, et al. Microvesicle-associated AAV vector as a novel gene delivery system.Mol Ther. 2012;20:960–71. [DOI] [PubMed] [PMC]
György B, Sage C, Indzhykulian AA, Scheffer DI, Brisson AR, Tan S, et al. Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV.Mol Ther. 2017;25:379–91. [DOI] [PubMed] [PMC]
Hudry E, Martin C, Gandhi S, György B, Scheffer DI, Mu D, et al. Exosome-associated AAV vector as a robust and convenient neuroscience tool.Gene Ther. 2016;23:380–92. [DOI] [PubMed] [PMC]
Meliani A, Leborgne C, Triffault S, Jeanson-Leh L, Veron P, Mingozzi F. Determination of anti-adeno-associated virus vector neutralizing antibody titer with an in vitro reporter system.Hum Gene Ther Methods. 2015;26:45–53. [DOI] [PubMed] [PMC]
György B, Maguire CA. Extracellular vesicles: nature’s nanoparticles for improving gene transfer with adeno-associated virus vectors.Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2018;10:e1488. [DOI] [PubMed]
Lewis ND, Sia CL, Kirwin K, Haupt S, Mahimkar G, Zi T, et al. Exosome Surface Display of IL12 Results in Tumor-Retained Pharmacology with Superior Potency and Limited Systemic Exposure Compared with Recombinant IL12.Mol Cancer Ther. 2021;20:523–34. [DOI] [PubMed]
Escudier B, Dorval T, Chaput N, André F, Caby MP, Novault S, et al. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial.J Transl Med. 2005;3:10. [DOI] [PubMed] [PMC]
Besse B, Charrier M, Lapierre V, Dansin E, Lantz O, Planchard D, et al. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC.Oncoimmunology. 2015;5:e1071008. [DOI] [PubMed] [PMC]
Herman S, Fishel I, Offen D. Intranasal delivery of mesenchymal stem cells-derived extracellular vesicles for the treatment of neurological diseases.Stem Cells. 2021;39:1589–600. [DOI] [PubMed]
Yao X, Lyu P, Yoo K, Yadav MK, Singh R, Atala A, et al. Engineered extracellular vesicles as versatile ribonucleoprotein delivery vehicles for efficient and safe CRISPR genome editing.J Extracell Vesicles. 2021;10:e12076. [DOI] [PubMed] [PMC]
Akyuz E, Aslan FS, Gokce E, Ilmaz O, Topcu F, Kakac S. Extracellular vesicle and CRISPR gene therapy: Current applications in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease.Eur J Neurosci. 2024;60:6057–90. [DOI] [PubMed]
Bang OY, Kim EH, Cho YH, Oh MJ, Chung JW, Chang WH, et al. Circulating Extracellular Vesicles in Stroke Patients Treated With Mesenchymal Stem Cells: A Biomarker Analysis of a Randomized Trial.Stroke. 2022;53:2276–86. [DOI] [PubMed]
Son JP, Kim EH, Shin EK, Kim DH, Sung JH, Oh MJ, et al. Mesenchymal Stem Cell-Extracellular Vesicle Therapy for Stroke: Scalable Production and Imaging Biomarker Studies.Stem Cells Transl Med. 2023;12:459–73. [DOI] [PubMed] [PMC]
Sánchez SV, Otavalo GN, Gazeau F, Silva AKA, Morales JO. Intranasal delivery of extracellular vesicles: A promising new approach for treating neurological and respiratory disorders.J Control Release. 2025;379:489–523. [DOI] [PubMed]
Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, 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. [DOI] [PubMed] [PMC]
Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes.Nat Biotechnol. 2011;29:341–5. [DOI] [PubMed]
Liu X, Cao Z, Wang W, Zou C, Wang Y, Pan L, et al. Engineered Extracellular Vesicle-Delivered CRISPR/Cas9 for Radiotherapy Sensitization of Glioblastoma.ACS Nano. 2023;17:16432–47. [DOI] [PubMed] [PMC]
Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, et al. Tumour exosome integrins determine organotropic metastasis.Nature. 2015;527:329–35. [DOI] [PubMed] [PMC]
Tian Y, Li S, Song J, Ji T, Zhu M, Anderson GJ, et al. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy.Biomaterials. 2014;35:2383–90. [DOI] [PubMed]
Kooijmans SAA, Fliervoet LAL, van der Meel R, Fens MHAM, Heijnen HFG, van Bergen En Henegouwen PMP, et al. PEGylated and targeted extracellular vesicles display enhanced cell specificity and circulation time.J Control Release. 2016;224:77–85. [DOI] [PubMed]
Qu M, Lin Q, Huang L, Fu Y, Wang L, He S, et al. Dopamine-loaded blood exosomes targeted to brain for better treatment of Parkinson's disease.J Control Release. 2018;287:156–66. [DOI] [PubMed]
Wang J, Chen D, Ho EA. Challenges in the development and establishment of exosome-based drug delivery systems.J Control Release. 2021;329:894–906. [DOI] [PubMed]
Lamichhane TN, Jeyaram A, Patel DB, Parajuli B, Livingston NK, Arumugasaamy N, et al. Oncogene Knockdown via Active Loading of Small RNAs into Extracellular Vesicles by Sonication.Cell Mol Bioeng. 2016;9:315–24. [DOI] [PubMed] [PMC]
Piffoux M, Silva AKA, Wilhelm C, Gazeau F, Tareste D. Modification of Extracellular Vesicles by Fusion with Liposomes for the Design of Personalized Biogenic Drug Delivery Systems.ACS Nano. 2018;12:6830–42. [DOI] [PubMed]
Herrmann IK, Wood MJA, Fuhrmann G. Extracellular vesicles as a next-generation drug delivery platform.Nat Nanotechnol. 2021;16:748–59. [DOI] [PubMed]
Yang D, Zhang W, Zhang H, Zhang F, Chen L, Ma L, et al. Progress, opportunity, and perspective on exosome isolation—efforts for efficient exosome-based theranostics.Theranostics. 2020;10:3684–707. [DOI] [PubMed] [PMC]
van de Wakker SI, Meijers FM, Sluijter JPG, Vader P. Extracellular Vesicle Heterogeneity and Its Impact for Regenerative Medicine Applications.Pharmacol Rev. 2023;75:1043–61. [DOI] [PubMed]
Allelein S, Medina-Perez P, Lopes ALH, Rau S, Hause G, Kölsch A, et al. Potential and challenges of specifically isolating extracellular vesicles from heterogeneous populations.Sci Rep. 2021;11:11585. [DOI] [PubMed] [PMC]
Patel GK, Khan MA, Zubair H, Srivastava SK, Khushman M, Singh S, et al. Comparative analysis of exosome isolation methods using culture supernatant for optimum yield, purity and downstream applications.Sci Rep. 2019;9:5335. [DOI] [PubMed] [PMC]
Liangsupree T, Multia E, Riekkola ML. Modern isolation and separation techniques for extracellular vesicles.J Chromatogr A. 2021;1636:461773. [DOI] [PubMed]
Williams S, Fernandez-Rhodes M, Law A, Peacock B, Lewis MP, Davies OG. Comparison of extracellular vesicle isolation processes for therapeutic applications.J Tissue Eng. 2023;14:20417314231174609. [DOI] [PubMed] [PMC]
Sharma S, LeClaire M, Wohlschlegel J, Gimzewski J. Impact of isolation methods on the biophysical heterogeneity of single extracellular vesicles.Sci Rep. 2020;10:13327. [DOI] [PubMed] [PMC]
Patel DB, Gray KM, Santharam Y, Lamichhane TN, Stroka KM, Jay SM. Impact of cell culture parameters on production and vascularization bioactivity of mesenchymal stem cell-derived extracellular vesicles.Bioeng Transl Med. 2017;2:170–9. [DOI] [PubMed] [PMC]
Rankin-Turner S, Vader P, O’Driscoll L, Giebel B, Heaney LM, Davies OG. A call for the standardised reporting of factors affecting the exogenous loading of extracellular vesicles with therapeutic cargos.Adv Drug Deliv Rev. 2021;173:479–91. [DOI] [PubMed] [PMC]
Burrello J, Monticone S, Gai C, Gomez Y, Kholia S, Camussi G. Stem Cell-Derived Extracellular Vesicles and Immune-Modulation.Front Cell Dev Biol. 2016;4:83. [DOI] [PubMed] [PMC]
Almeria C, Kreß S, Weber V, Egger D, Kasper C. Heterogeneity of mesenchymal stem cell-derived extracellular vesicles is highly impacted by the tissue/cell source and culture conditions.Cell Biosci. 2022;12:51. [DOI] [PubMed] [PMC]
Jeppesen DK, Fenix AM, Franklin JL, Higginbotham JN, Zhang Q, Zimmerman LJ, et al. Reassessment of Exosome Composition.Cell. 2019;177:428–45.e18. [DOI] [PubMed] [PMC]
Chen Y, Wu T, Zhu Z, Huang H, Zhang L, Goel A, et al. An integrated workflow for biomarker development using microRNAs in extracellular vesicles for cancer precision medicine.Semin Cancer Biol. 2021;74:134–55. [DOI] [PubMed]
Han KM, Ham BJ. How Inflammation Affects the Brain in Depression: A Review of Functional and Structural MRI Studies.J Clin Neurol. 2021;17:503–15. [DOI] [PubMed] [PMC]
Zhang X, Zhang H, Gu J, Zhang J, Shi H, Qian H, et al. Engineered Extracellular Vesicles for Cancer Therapy.Adv Mater. 2021;33:e2005709. [DOI] [PubMed]
Claridge B, Lozano J, Poh QH, Greening DW. Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities.Front Cell Dev Biol. 2021;9:734720. [DOI] [PubMed] [PMC]
Williams A, Branscome H, Kashanchi F, Batrakova EV. Targeting of Extracellular Vesicle-Based Therapeutics to the Brain.Cells. 2025;14:548. [DOI] [PubMed] [PMC]
Cherian SG, Narayan SK, Arumugam M. Exosome therapies improve outcome in rodents with ischemic stroke; meta-analysis.Brain Res. 2023;1803:148228. [DOI] [PubMed]
Yang Z, Liang Z, Rao J, Xie H, Zhou M, Xu X, et al. Hypoxic-preconditioned mesenchymal stem cell-derived small extracellular vesicles promote the recovery of spinal cord injury by affecting the phenotype of astrocytes through the miR-21/JAK2/STAT3 pathway.CNS Neurosci Ther. 2024;30:e14428. [DOI] [PubMed] [PMC]
Kodali M, Madhu LN, Reger RL, Milutinovic B, Upadhya R, Gonzalez JJ, et al. Intranasally administered human MSC-derived extracellular vesicles inhibit NLRP3-p38/MAPK signaling after TBI and prevent chronic brain dysfunction.Brain Behav Immun. 2023;108:118–34. [DOI] [PubMed] [PMC]
Xue LX, Shu LY, Wang HM, Lu KL, Huang LG, Xiang JY, et al. miR-181b promotes angiogenesis and neurological function recovery after ischemic stroke.Neural Regen Res. 2023;18:1983–9. [DOI] [PubMed] [PMC]
Zhu X, Liu Q, Zhu F, Jiang R, Lu Z, Wang C, et al. An engineered cellular carrier delivers miR-138-5p to enhance mitophagy and protect hypoxic-injured neurons via the DNMT3A/Rhebl1 axis.Acta Biomater. 2024;186:424–38. [DOI] [PubMed]
Putthanbut N, Lee JY, Borlongan CV. Extracellular vesicle therapy in neurological disorders.J Biomed Sci. 2024;31:85. [DOI] [PubMed] [PMC]
Choi HK, Chen M, Goldston LL, Lee K. Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions.Nano Converg. 2024;11:19. [DOI] [PubMed] [PMC]
Fernandes M, Lopes I, Magalhães L, Sárria MP, Machado R, Sousa JC, et al. Novel concept of exosome-like liposomes for the treatment of Alzheimer's disease.J Control Release. 2021;336:130–43. [DOI] [PubMed]
Nieland L, Mahjoum S, Grandell E, Breyne K, Breakefield XO. Engineered EVs designed to target diseases of the CNS.J Control Release. 2023;356:493–506. [DOI] [PubMed] [PMC]
Shahjin F, Chand S, Yelamanchili SV. Extracellular Vesicles as Drug Delivery Vehicles to the Central Nervous System.J Neuroimmune Pharmacol. 2020;15:443–58. [DOI] [PubMed]
Guo Y, Hu D, Lian L, Zhao L, Li M, Bao H, et al. Stem Cell-derived Extracellular Vesicles: A Promising Nano Delivery Platform to the Brain?Stem Cell Rev Rep. 2023;19:285–308. [DOI] [PubMed]
Kumar A, Nader MA, Deep G. Emergence of Extracellular Vesicles as “Liquid Biopsy” for Neurological Disorders: Boom or Bust.Pharmacol Rev. 2024;76:199–227. [DOI] [PubMed] [PMC]
Chatterjee M, Özdemir S, Fritz C, Möbius W, Kleineidam L, Mandelkow E, et al. Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS.Nat Med. 2024;30:1771–83. [DOI] [PubMed] [PMC]
Katsu M, Hama Y, Utsumi J, Takashina K, Yasumatsu H, Mori F, et al. MicroRNA expression profiles of neuron-derived extracellular vesicles in plasma from patients with amyotrophic lateral sclerosis.Neurosci Lett. 2019;708:134176. [DOI] [PubMed]
Honorato-Mauer J, Xavier G, Ota VK, Chehimi SN, Mafra F, Cuóco C, et al. Alterations in microRNA of extracellular vesicles associated with major depression, attention-deficit/hyperactivity and anxiety disorders in adolescents.Transl Psychiatry. 2023;13:47. [DOI] [PubMed] [PMC]
Chudzik A, Śledzianowski A, Przybyszewski AW. Machine Learning and Digital Biomarkers Can Detect Early Stages of Neurodegenerative Diseases.Sensors (Basel). 2024;24:1572. [DOI] [PubMed] [PMC]
Whitley JA, Cai H. Engineering extracellular vesicles to deliver CRISPR ribonucleoprotein for gene editing.J Extracell Vesicles. 2023;12:e12343. [DOI] [PubMed] [PMC]
Pauwels MJ, Vandendriessche C, Vandenbroucke RE. Special delEVery: Extracellular Vesicles as Promising Delivery Platform to the Brain.Biomedicines. 2021;9:1734. [DOI] [PubMed] [PMC]
Li Z, Wang X, Wang X, Yi X, Wong YK, Wu J, et al. Research progress on the role of extracellular vesicles in neurodegenerative diseases.Transl Neurodegener. 2023;12:43. [DOI] [PubMed] [PMC]
Polanco JC, Scicluna BJ, Hill AF, Götz J. Extracellular Vesicles Isolated from the Brains of rTg4510 Mice Seed Tau Protein Aggregation in a Threshold-dependent Manner.J Biol Chem. 2016;291:12445–66. [DOI] [PubMed] [PMC]
Reed SL, Escayg A. Extracellular vesicles in the treatment of neurological disorders.Neurobiol Dis. 2021;157:105445. [DOI] [PubMed] [PMC]
Yang Z, Liang Z, Rao J, Lin F, Lin Y, Xu X, et al. Mesenchymal stem cell-derived extracellular vesicles therapy in traumatic central nervous system diseases: a systematic review and meta-analysis.Neural Regen Res. 2023;18:2406–12. [DOI] [PubMed] [PMC]
Yan B, Liao P, Liu Y, Han Z, Wang C, Chen F, et al. Therapeutic potential of microglia-derived extracellular vesicles in ischemic stroke.Int Immunopharmacol. 2024;139:112712. [DOI] [PubMed]
Li T, Yang Y, Qi H, Cui W, Zhang L, Fu X, et al. CRISPR/Cas9 therapeutics: progress and prospects.Signal Transduct Target Ther. 2023;8:36. [DOI] [PubMed] [PMC]
Mun D, Kang JY, Kim H, Yun N, Joung B. Small extracellular vesicle-mediated CRISPR-Cas9 RNP delivery for cardiac-specific genome editing.J Control Release. 2024;370:798–810. [DOI] [PubMed]
Lin J, Jia S, Jiao Z, Chen J, Li W, Cao F, et al. Global research trends in CRISPR-related technologies associated with extracellular vesicles from 2015 to 2022: a bibliometric, dynamic, and visualized study.Cell Mol Biol Lett. 2023;28:99. [DOI] [PubMed] [PMC]
Greenberg ZF, Graim KS, He M. Towards artificial intelligence-enabled extracellular vesicle precision drug delivery.Adv Drug Deliv Rev. 2023;199:114974. [DOI] [PubMed]
Belkozhayev AM, Al-Yozbaki M, George A, Ye Niyazova R, Sharipov KO, Byrne LJ, et al. Extracellular Vesicles, Stem Cells and the Role of miRNAs in Neurodegeneration.Curr Neuropharmacol. 2022;20:1450–78. [DOI] [PubMed] [PMC]
Sprincl V, Romanyuk N. miRNA in blood-brain barrier repair: role of extracellular vesicles in stroke recovery.Front Cell Neurosci. 2025;19:1503193. [DOI] [PubMed] [PMC]