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Role of Exosomes in Multiple Sclerosis

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Exosomes Based Drug Delivery Strategies for Brain Disorders

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Abstract

Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune disease in which autoreactive immune cells recognize myelin antigens and cause demyelination and axonal damage. Inflammatory CD4+ T cells that are responsive to myelin peptides primarily recognize myelin and oligodendrocytes as their targets. Regulatory CD4+ T (Treg) cells typically maintain immune system homeostasis by blocking the negative effects of inflammatory T cells. However, for an unknown reason, Treg cell numbers are lower in MS patients. Particularly those underlying the start of immune system dysfunction, mechanisms important to the MS pathogenesis have not yet been fully understood. For instance, the peripheral immune system’s mechanism for producing reactivity to CNS components is unknown. This commentary focuses on a unique way that exosomes in the bloodstream operate in multiple sclerosis (MS): they prevent Treg cells from differentiating. According to recent findings, exosomes are endosome-derived microvesicles that are 30–200 nm in size and carry specialized protein and RNA cargo. These cells are thought to release these exosomes. The idea that exosomes could influence signalling between brain cells and enhance the distribution of bioactive substances is raised by the fact that exosomes can interact with nearby cells. In addition to myelinating axons, oligodendrocytes also preserve axonal integrity via an unidentified trophic support mechanism. These exosomes stimulate pre-oligodendrocytes to develop into myelin-producing cells in the brain, greatly increasing myelination and improving demyelination after damage. They also have a high potential as a treatment since they are non-toxic and quickly traverse the blood–brain barrier. A novel perspective on the study of the pathophysiology of this disease should be offered by increased knowledge of exosome-dependent pathways in MS. Exosomes and their contents may function as biomarkers in MS.

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References

  • Aghebati-Maleki A, Nami S, Baghbanzadeh A, Karzar BH, Noorolyai S, Fotouhi A, Aghebati-Maleki L (2019) Implications of exosomes as diagnostic and therapeutic strategies in cancer. J Cell Physiol 234(12):21694–21706

    Article  CAS  PubMed  Google Scholar 

  • Alyamani H, Obeid MA, Tate RJ, Ferro VA (2019) Exosomes: fighting cancer with cancer. Ther Deliv 10(1):37–61

    Article  CAS  PubMed  Google Scholar 

  • Ananbeh H, Vodicka P, Kupcova Skalnikova H (2021) Emerging roles of exosomes in Huntington’s disease. Int J Mol Sci 22(8):4085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aryani A, Denecke B (2016) Exosomes as a nanodelivery system: a key to the future of neuromedicine? Mol Neurobiol 53:818–834

    Article  CAS  PubMed  Google Scholar 

  • Azimi M, Ghabaee M, Moghadasi AN, Izad M (2019) Altered expression of miR-326 in T cell-derived exosomes of patients with relapsing-remitting multiple sclerosis. Iran J Allergy Asthma Immunol 24:108–113

    Google Scholar 

  • Bakhti M, Winter C, Simons M (2011) Inhibition of myelin membrane sheath formation by oligodendrocyte-derived exosome-like vesicles. J Biol Chem 286(1):787–796

    Article  CAS  PubMed  Google Scholar 

  • Broekman ML, Maas SL, Abels ER, Mempel TR, Krichevsky AM, Breakefield XO (2018) Multidimensional communication in the microenvirons of glioblastoma. Nat Rev Neurol 14(8):482–495

    Article  PubMed  PubMed Central  Google Scholar 

  • Bu H, He D, He X, Wang K (2019) Exosomes: isolation, analysis, and applications in cancer detection and therapy. Chembiochem 20(4):451–461

    Article  CAS  PubMed  Google Scholar 

  • Chitnis T, Prat A, Mycko MP, Baranzini SE (2020) microRNA and exosome profiling in multiple sclerosis. Mult Scler J 26(5)

    Google Scholar 

  • Das S, Abdel-Mageed AB, Adamidi C, Adelson PD, Akat KM, Alsop E, Ansel KM, Arango J, Aronin N, Avsaroglu SK, Azizian A (2019) The extracellular RNA communication consortium: establishing foundational knowledge and technologies for extracellular RNA research. Cell 177(2):231–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Toro J, Herschlik L, Waldner C, Mongini C (2015) Emerging roles of exosomes in normal and pathological conditions: new insights for diagnosis and therapeutic applications. Front Immunol 6:203

    PubMed  PubMed Central  Google Scholar 

  • Dobson R, Giovannoni G (2019) Multiple sclerosis – a review. Eur J Neurol 26(1):27–40

    Article  CAS  PubMed  Google Scholar 

  • Dyment DA, Ebers GC, Sadovnick AD (2004) Genetics of multiple sclerosis. Lancet Neurol 3(2):104–110

    Article  CAS  PubMed  Google Scholar 

  • Ebers GC (2008) Environmental factors and multiple sclerosis. Lancet Neurol 7(3):268–277

    Article  PubMed  Google Scholar 

  • Feinstein A (2004) The neuropsychiatry of multiple sclerosis. Can J Psychiatry 49(3):157–163

    Article  PubMed  Google Scholar 

  • Fröhlich D, Kuo WP, Frühbeis C, Sun JJ, Zehendner CM, Luhmann HJ, Pinto S, Toedling J, Trotter J, Krämer-Albers EM (2014) Multifaceted effects of oligodendroglial exosomes on neurons: impact on neuronal firing rate, signal transduction and gene regulation. Philos Trans R Soc B Biol Sci 369(1652):20130510

    Article  Google Scholar 

  • Gold R, Wolinsky JS (2011) Pathophysiology of multiple sclerosis and the place of teriflunomide. Acta Neurol Scand 124(2):75–84

    Article  CAS  PubMed  Google Scholar 

  • Graner MW, Schnell S, Olin MR (2018) Tumor-derived exosomes, microRNAs, and cancer immune suppression. In: Seminars in immunopathology, vol 40. Springer, Berlin Heidelberg, pp 505–515

    Google Scholar 

  • Greenfield AL, Hauser SL (2018) B-cell therapy for multiple sclerosis: entering an era. Ann Neurol 83(1):13–26

    Article  PubMed  PubMed Central  Google Scholar 

  • He M, Zhang HN, Tang ZC, Gao SG (2021) Diagnostic and therapeutic potential of exosomal microRNAs for neurodegenerative diseases. Neural Plast 2021:1–3

    Article  CAS  Google Scholar 

  • Jeppesen DK, Fenix AM, Franklin JL, Higginbotham JN, Zhang Q, Zimmerman LJ, Liebler DC, ** J, Liu Q, Evans R, Fissell WH (2019) Reassessment of exosome composition. Cell 177(2):428–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang H, Li Z, Li X, **a J (2015) Intercellular transfer of messenger RNAs in multiorgan tumorigenesis by tumor cell-derived exosomes. Mol Med Rep 11(6):4657–4663

    Article  CAS  PubMed  Google Scholar 

  • Kalluri R (2016) The biology and function of exosomes in cancer. J Clin Invest 126(4):1208–1215

    Article  PubMed  PubMed Central  Google Scholar 

  • Karami Fath M, Azami J, Jaafari N, Akbari Oryani M, Jafari N, Azargoonjahromi A, Nabi-Afjadi M, Payandeh Z, Zalpoor H, Shanehbandi D (2022) Exosome application in treatment and diagnosis of B-cell disorders: leukemias, multiple sclerosis, and arthritis rheumatoid. Cell Mol Biol Lett 27(1):1–28

    Article  Google Scholar 

  • Korkut C, Li Y, Koles K, Brewer C, Ashley J, Yoshihara M, Budnik V (2013) Regulation of postsynaptic retrograde signaling by presynaptic exosome release. Neuron 77(6):1039–1046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krieger S, Sorrells SF, Nickerson M, Pace TW (2014) Mechanistic insights into corticosteroids in multiple sclerosis: war horse or chameleon?☆. Clin Neurol Neurosurg 119:6–16

    Article  PubMed  Google Scholar 

  • Lee J, McKinney KQ, Pavlopoulos AJ, Han MH, Kim SH, Kim HJ, Hwang S (2016) Exosomal proteome analysis of cerebrospinal fluid detects biosignatures of neuromyelitis optica and multiple sclerosis. Clin Chim Acta (462):118–126

    Google Scholar 

  • Leray E, Yaouanq J, Le Page E, Coustans M, Laplaud D, Oger J, Edan G (2010) Evidence for a two-stage disability progression in multiple sclerosis. Brain 133(7):1900–1913

    Article  PubMed  PubMed Central  Google Scholar 

  • Pieragostino D, Cicalini I, Lanuti P, Ercolino E, di Ioia M, Zucchelli M, Zappacosta R, Miscia S, Marchisio M, Sacchetta P, Onofrj M (2018) Enhanced release of acid sphingomyelinase-enriched exosomes generates a lipidomics signature in CSF of multiple sclerosis patients. Sci Rep 8(1):3071

    Article  PubMed  PubMed Central  Google Scholar 

  • Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69(2):292–302

    Article  PubMed  PubMed Central  Google Scholar 

  • Ponomarev ED, Veremeyko T, Barteneva N, Krichevsky AM, Weiner HL (2011) MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-α–PU. 1 pathway. Nat Med 17(1):64–70

    Article  CAS  PubMed  Google Scholar 

  • Pregnolato F, Cova L, Doretti A, Bardelli D, Silani V, Bossolasco P (2021) Exosome microRNAs in amyotrophic lateral sclerosis: a pilot study. Biomol Ther 11(8):1220

    CAS  Google Scholar 

  • Pusic AD, Pusic KM, Kraig RP (2014) What are exosomes and how can they be used in multiple sclerosis therapy? Expert Rev Neurother 14(4):353–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raine CS, Bonetti B, Cannella B (1998) Multiple sclerosis: expression of molecules of the tumor necrosis factor ligand and receptor families in relationship to the demyelinated plaque. Rev Neurol 154(8–9):577–585

    CAS  PubMed  Google Scholar 

  • Raposo G, Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200(4):373–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, Geuze HJ (1996) B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183(3):1161–1172

    Article  CAS  PubMed  Google Scholar 

  • Sáenz-Cuesta M, Irizar H, Castillo-Triviño T, Muñoz-Culla M, Osorio-Querejeta I, Prada A, Sepúlveda L, López-Mato MP, De Munain AL, Comabella M, Villar LM (2014) Circulating microparticles reflect treatment effects and clinical status in multiple sclerosis. Biomark Med 8(5):653–661

    Article  PubMed  Google Scholar 

  • Salarpour S, Barani M, Pardakhty A, Khatami M, Chauhan NP (2022) The application of exosomes and exosome-nanoparticle in treating brain disorders. J Mol Liq 19:118549

    Article  Google Scholar 

  • Schneider A, Simons M (2013) Exosomes: vesicular carriers for intercellular communication in neurodegenerative disorders. Cell Tissue Res 352:33–47

    Article  CAS  PubMed  Google Scholar 

  • Selmaj I, Mycko MP, Raine CS, Selmaj KW (2017) The role of exosomes in CNS inflammation and their involvement in multiple sclerosis. J Neuroimmunol 306:1–10

    Article  CAS  PubMed  Google Scholar 

  • Shamili FH, Alibolandi M, Rafatpanah H, Abnous K, Mahmoudi M, Kalantari M, Taghdisi SM, Ramezani M (2019) Immunomodulatory properties of MSC-derived exosomes armed with high affinity aptamer toward mylein as a platform for reducing multiple sclerosis clinical score. J Control Release 299:149–164

    Article  Google Scholar 

  • Sharma P, Schiapparelli L, Cline HT (2013) Exosomes function in cell–cell communication during brain circuit development. Curr Opin Neurobiol 23(6):997–1004

    Article  CAS  PubMed  Google Scholar 

  • Singh J, Deshpande M, Suhail H, Rattan R, Giri S (2016) Targeted stage-specific inflammatory microRNA profiling in urine during disease progression in experimental autoimmune encephalomyelitis: markers of disease progression and drug response. J Neuroimmune Pharmacol 11(1):84–97

    Article  PubMed  Google Scholar 

  • Smalheiser NR (2007) Exosomal transfer of proteins and RNAs at synapses in the nervous system. Biol Direct 2(1):1–5

    Article  Google Scholar 

  • Smith KJ (2006) Pathophysiology of multiple sclerosis. Rev Prat 56(12):1299–1303

    PubMed  Google Scholar 

  • Smith KJ, McDonald WI (1999) The pathophysiology of multiple sclerosis⋮ the mechanisms underlying the production of symptoms and the natural history of the disease. Philos Trans R Soc Lond B Biol Sci 354(1390):1649–1673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sospedra M, Martin R (2005) Immunology of multiple sclerosis. Annu Rev Immunol 23:683–747

    Article  CAS  PubMed  Google Scholar 

  • Théry C, Zitvogel L, Amigorena S (2002) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2(8):569–579

    Article  PubMed  Google Scholar 

  • Tkach M, Théry C (2016) Communication by extracellular vesicles: where we are and where we need to go. Cell 164(6):1226–1232

    Article  CAS  PubMed  Google Scholar 

  • Tsilioni I, Panagiotidou S, Theoharides TC (2014) Exosomes in neurologic and psychiatric disorders. Clin Ther 36(6):882–888

    Article  CAS  PubMed  Google Scholar 

  • Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6):654–659

    Article  CAS  PubMed  Google Scholar 

  • Verderio C, Muzio L, Turola E, Bergami A, Novellino L, Ruffini F, Riganti L, Corradini I, Francolini M, Garzetti L, Maiorino C (2012) Myeloid microvesicles are a marker and therapeutic target for neuroinflammation. Ann Neurol 72(4):610–624

    Article  CAS  PubMed  Google Scholar 

  • Vincent-Schneider H, Stumptner-Cuvelette P, Lankar D, Pain S, Raposo G, Benaroch P, Bonnerot C (2002) Exosomes bearing HLA-DR1 molecules need dendritic cells to efficiently stimulate specific T cells. Int Immunol 14(7):713–722

    Article  CAS  PubMed  Google Scholar 

  • Wang S, Cesca F, Loers G, Schweizer M, Buck F, Benfenati F, Schachner M, Kleene R (2011) 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 31(20):7275–7290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wheway J, Latham SL, Combes V, Grau GE (2014) Endothelial microparticles interact with and support the proliferation of T cells. J Immunol 193(7):3378–3387

    Article  CAS  PubMed  Google Scholar 

  • Williams JL, Gatson NN, Smith KM, Almad A, McTigue DM, Whitacre CC (2013) Serum exosomes in pregnancy-associated immune modulation and neuroprotection during CNS autoimmunity. Clin Immunol 149(2):236–243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu X, Zheng T, Zhang B (2017) Exosomes in Parkinson’s disease. Neurosci Bull 33:331–338

    Article  CAS  PubMed  Google Scholar 

  • Xu R, Rai A, Chen M, Suwakulsiri W, Greening DW, Simpson RJ (2018) Extracellular vesicles in cancer—implications for future improvements in cancer care. Nat Rev Clin Oncol 15(10):617–638

    Article  CAS  PubMed  Google Scholar 

  • Yu L, Yang F, Jiang L, Chen Y, Wang K, Xu F, Wei Y, Cao X, Wang J, Cai Z (2013) Exosomes with membrane-associated TGF-β1 from gene-modified dendritic cells inhibit murine EAE independently of MHC restriction. Eur J Immunol 43(9):2461–2472

    Article  CAS  PubMed  Google Scholar 

  • Zhuang X, **ang X, Grizzle W, Sun D, Zhang S, Axtell RC, Ju S, Mu J, Zhang L, Steinman L, Miller D (2011) Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther 19(10):1769–1779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. School of Medical & Allied Sciences, K.R. Mangalam University, Gurugram, Haryana, India

    Yash Jasoria, Mohit Agrawal & Hema Chaudhary

  2. Faculty of Pharmacy, DIT University, Dehradun, Uttrakhand, India

    Manmohan Singhal

  3. School of Medical & Allied Sciences, G.D. Goenka University, Gurugram, Haryana, India

    Manish Yadav

  4. School of Pharmaceutical Sciences, Jaipur National University, Jaipur, Rajasthan, India

    Md Sadique Hussain

  5. School of Pharmacy, Noida International University, Greater Noida, UP, India

    Sameer Rastogi

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  1. Yash Jasoria
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  2. Mohit Agrawal
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  3. Manmohan Singhal
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  5. Manish Yadav
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  6. Md Sadique Hussain
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  7. Sameer Rastogi
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Editors and Affiliations

  1. Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University Madhya Pradesh, Gwalior, Madhya Pradesh, India

    Neeraj Mishra

  2. Department of Pharmaceutical Sciences, Bengal College of Pharmaceutical Sciences & Research, Durgapur, West Bengal, India

    Sumel Ashique

  3. Department of Pharmaceutics, Guru Ramdas Khalsa Institute, Jabalpur, Madhya Pradesh, India

    Ashish Garg

  4. University of Michigan Medical Center, Ann Arbor, MI, USA

    Vadivalagan Chithravel

  5. Department of Chemical Pathology, School of Pathology, University of the Free State (Bloemfontein Campus), Bloemfontein, Free State, South Africa

    Krishnan Anand

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Jasoria, Y. et al. (2024). Role of Exosomes in Multiple Sclerosis. In: Mishra, N., Ashique, S., Garg, A., Chithravel, V., Anand, K. (eds) Exosomes Based Drug Delivery Strategies for Brain Disorders. Springer, Singapore. https://doi.org/10.1007/978-981-99-8373-5_4

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  • DOI: https://doi.org/10.1007/978-981-99-8373-5_4

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