Application of exosomes in the diagnosis and treatment of epilepsy_Journal of Epilepsy

Authors：

LU Qian ^1,2 , ZHANG Qi ^1,2 , WANG Qiuhong ^1,2 , DUN Shuo ^1,2 , WANG Jia ^1,2 ,  ZOU Liping ^1,2

1. Medical School of Chinese PLA, Beijing 100853, China;
2. Department of Pediatrics, the First Medical Center of PLA General Hospital, Beijing 100853, China;

Corresponding author：

ZOU Liping, Email: zouliping21@sina.com

Keywords：

Exosomes; Epilepsy; Diagnosis; Treatment

DOI：

10.7507/2096-0247.202304010

Video：

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Epilepsy is a common neurological disease with complex etiology and various seizure forms. It can affect people of all ages. Although a variety of antiseizure medications are available, one-third of patients still have poor drug treatment. Therefore, better methods for the diagnosis and treatment of epilepsy are particularly important. Exosomes are extracellular vesicles with a diameter of 30 ~ 150 nm that have powerful intercellular information transmission functions and also play an important role in the central nervous system. Exosomes released by nerve cells in the local microenvironment can participate in nerve development and plasticity, regulate neuroinflammation, and reduce neuronal loss. Moreover, some proteins or micro ribonucleic acid (miRNA) in exosomes are highly correlated with epilepsy and are changed in epileptogenesis, so they play an important role in the prevention and early diagnosis of epilepsy. In addition, exosomes have better biocompatibility and lower immunogenicity. Its small size can effectively avoid the phagocytosis of mononuclear macrophages. Moreover, the proteins carried on its surface have a strong homing ability to target tissues or cells and can penetrate the blood-brain barrier to the intracranial, so exosomes have the advantage of natural drug delivery. Therefore, this study reviews the application of exosomes in epilepsy to improve the understanding of exosomes in scientific research and clinical workers.

Citation： LU Qian, ZHANG Qi, WANG Qiuhong, DUN Shuo, WANG Jia, ZOU Liping. Application of exosomes in the diagnosis and treatment of epilepsy. Journal of Epilepsy, 2023, 9(4): 306-309. doi: 10.7507/2096-0247.202304010 Copy

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10.	Valadi H, Ekström K, Bossios A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature Cell Biology, 2007, 9(6): 654-659.
11.	Lu TX, Rothenberg ME. MicroRNA. The Journal of Allergy and Clinical Immunology, 2018, 141(4): 1202-1207.
12.	Yu Y, Hou K, Ji T, et al. The role of exosomal microRNAs in central nervous system diseases. Molecular and Cellular Biochemistry, 2021, 476(5): 2111-2124.
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14.	Kumari M, Anji A. Small but mighty-exosomes, novel intercellular messengers in neurodegeneration. Biology, 2022, 11(3): 123-126.
15.	Xiao L, Hareendran S, Loh YP. Function of exosomes in neurological disorders and brain tumors. Extracellular Vesicles and Circulating Nucleic Acids, 2021, 2: 55-79.
16.	Liu HY, Huang CM, Hung YF, et al. The microRNAs Let7c and miR21 are recognized by neuronal Toll-like receptor 7 to restrict dendritic growth of neurons. Experimental Neurology, 2015, 269: 202-12.
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19.	Krämer-Albers EM. Superfood for axons: glial exosomes boost axonal energetics by delivery of SIRT2. Neuron, 2021, 109(21): 3397-3400.
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27.	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(8): 126201.
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29.	Liu Y, Yu G, Ding YY, et al. Expression of miR-155 in serum exosomes in children with epilepsy and its diagnostic value. Disease Markers, 2022, 22: 7979500.
30.	Zhang Y, Bi J, Huang J, et al. Exosome: a review of its classification, isolation techniques, storage, diagnostic and targeted therapy applications. International Journal of Nanomedicine, 2020, 15: 6917-6934.
31.	Yin S, Ji C, Wu P, et al. Human umbilical cord mesenchymal stem cells and exosomes: bioactive ways of tissue injury repair. American Journal of Translational Research, 2019, 11(3): 1230-1240.
32.	Heo J, Kang H. Exosome-based treatment for atherosclerosis. International Journal of Molecular Sciences, 2022, 23(2): 652-661.
33.	Kanchanapally R, Deshmukh SK, Chavva SR, et al. Drug-loaded exosomal preparations from different cell types exhibit distinctive loading capability, yield, and antitumor efficacies: a comparative analysis. International Journal of Nanomedicine, 2019, 14: 531-541.
34.	Zhang H, Wang L, Li C, et al. Exosome-induced regulation in inflammatory bowel disease. Frontiers in Immunology, 2019, 10: 1464.
35.	Kodali M, Castro OW, Kim DK, et al. Intranasally administered human msc-derived extracellular vesicles pervasively incorporate into neurons and microglia in both intact and status epilepticus injured forebrain. International Journal of Molecular Sciences, 2019, 21(1): 235-238.
36.	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. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114(17): e3536-e3545.
37.	Xian P, Hei Y, Wang R, et al. Mesenchymal stem cell-derived exosomes as a nanotherapeutic agent for amelioration of inflammation-induced astrocyte alterations in mice. Theranostics, 2019, 9(20): 5956-5975.

1. Milligan TA. Epilepsy: a clinical overview. The American Journal of Medicine, 2021, 134(7): 840-7.
2. Thijs RD, Surges R, O'brien TJ, et al. Epilepsy in adults. Lancet (London, England), 2019, 393(10172): 689-701.
3. Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia, 2017, 58(4): 512-521.
4. Shahraki K, Boroumand PG, Lotfi H, et al. An update in the applications of exosomes in cancer theranostics: from research to clinical trials. Journal of Cancer Research and Clinical Oncology, 2023, 12(1): 152-163.
5. Johnstone RM, Adam M, Hammond JR, et al. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). The Journal of Biological Chemistry, 1987, 262(19): 9412-20.
6. Venturini A, Passalacqua M, Pelassa S, et al. Exosomes from astrocyte processes: signaling to neurons. Frontiers in pharmacology, 2019, 10: 1452.
7. Zhang Y, Xu C. Effects of exosomes on adult hippocampal neurogenesis and neuropsychiatric disorders. Molecular Biology Reports, 2022, 49(7): 6763-6777.
8. 高振橙, 刘欣. 间充质干细胞外泌体在神经系统疾病修复过程中的作用与应用. 中国组织工程研究, 2020, 24(19): 7.
9. He C, Zheng S, Luo Y, et al. Exosome theranostics: biology and translational medicine. Theranostics, 2018, 8(1): 237-255.
10. Valadi H, Ekström K, Bossios A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature Cell Biology, 2007, 9(6): 654-659.
11. Lu TX, Rothenberg ME. MicroRNA. The Journal of Allergy and Clinical Immunology, 2018, 141(4): 1202-1207.
12. Yu Y, Hou K, Ji T, et al. The role of exosomal microRNAs in central nervous system diseases. Molecular and Cellular Biochemistry, 2021, 476(5): 2111-2124.
13. Wei N, Zhang H, Wang J, et al. The progress in diagnosis and treatment of exosomes and micrornas on epileptic comorbidity depression. Frontiers in Psychiatry, 2020, 11: 405.
14. Kumari M, Anji A. Small but mighty-exosomes, novel intercellular messengers in neurodegeneration. Biology, 2022, 11(3): 123-126.
15. Xiao L, Hareendran S, Loh YP. Function of exosomes in neurological disorders and brain tumors. Extracellular Vesicles and Circulating Nucleic Acids, 2021, 2: 55-79.
16. Liu HY, Huang CM, Hung YF, et al. The microRNAs Let7c and miR21 are recognized by neuronal Toll-like receptor 7 to restrict dendritic growth of neurons. Experimental Neurology, 2015, 269: 202-12.
17. Ahmad S, Srivastava RK, Singh P, et al. Role of extracellular vesicles in glia-neuron intercellular communication. Frontiers in Molecular Neuroscience, 2022, 15: 844194.
18. Pei X, Li Y, Zhu L, et al. Astrocyte-derived exosomes suppress autophagy and ameliorate neuronal damage in experimental ischemic stroke. Experimental Cell Research, 2019, 382(2): 111474.
19. Krämer-Albers EM. Superfood for axons: glial exosomes boost axonal energetics by delivery of SIRT2. Neuron, 2021, 109(21): 3397-3400.
20. Ma Y, Li C, Huang Y, et al. Exosomes released from neural progenitor cells and induced neural progenitor cells regulate neurogenesis through miR-21a. Cell Communication and Signaling, 2019, 17(1): 96.
21. Sharma P, Mesci P, Carromeu C, et al. Exosomes regulate neurogenesis and circuit assembly. Proceedings of the National Academy of Sciences of the United States of America, 2019, 116(32): 16086-16094.
22. Batool A, Hill TDM, Nguyen NT, et al. Altered biogenesis and microRNA content of hippocampal exosomes following experimental status epilepticus. Frontiers in Neuroscience, 2019, 13: 1404.
23. Lin Z, Gu Y, Zhou R, et al. Serum exosomal proteins F9 and TSP-1 as potential diagnostic biomarkers for newly diagnosed epilepsy. Frontiers in Neuroscience, 2020, 14: 737.
24. Gitaí DLG, Dos Santos YDR, Upadhya R, et al. Extracellular vesicles in the forebrain display reduced miR-346 and miR-331-3p in a rat model of chronic temporal lobe epilepsy. Molecular Neurobiology, 2020, 57(3): 1674-1687.
25. 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(3): 4136-4146.
26. Raoof R, Bauer S, El Naggar H, et al. Dual-center, dual-platform microRNA profiling identifies potential plasma biomarkers of adult temporal lobe epilepsy. EBioMedicine, 2018, 38: 127-141.
27. 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(8): 126201.
28. Martins-Ferreira R, Chaves J, Carvalho C, et al. Circulating microRNAs as potential biomarkers for genetic generalized epilepsies: a three microRNA panel. European Journal of Neurology, 2020, 27(4): 660-666.
29. Liu Y, Yu G, Ding YY, et al. Expression of miR-155 in serum exosomes in children with epilepsy and its diagnostic value. Disease Markers, 2022, 22: 7979500.
30. Zhang Y, Bi J, Huang J, et al. Exosome: a review of its classification, isolation techniques, storage, diagnostic and targeted therapy applications. International Journal of Nanomedicine, 2020, 15: 6917-6934.
31. Yin S, Ji C, Wu P, et al. Human umbilical cord mesenchymal stem cells and exosomes: bioactive ways of tissue injury repair. American Journal of Translational Research, 2019, 11(3): 1230-1240.
32. Heo J, Kang H. Exosome-based treatment for atherosclerosis. International Journal of Molecular Sciences, 2022, 23(2): 652-661.
33. Kanchanapally R, Deshmukh SK, Chavva SR, et al. Drug-loaded exosomal preparations from different cell types exhibit distinctive loading capability, yield, and antitumor efficacies: a comparative analysis. International Journal of Nanomedicine, 2019, 14: 531-541.
34. Zhang H, Wang L, Li C, et al. Exosome-induced regulation in inflammatory bowel disease. Frontiers in Immunology, 2019, 10: 1464.
35. Kodali M, Castro OW, Kim DK, et al. Intranasally administered human msc-derived extracellular vesicles pervasively incorporate into neurons and microglia in both intact and status epilepticus injured forebrain. International Journal of Molecular Sciences, 2019, 21(1): 235-238.
36. 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. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114(17): e3536-e3545.
37. Xian P, Hei Y, Wang R, et al. Mesenchymal stem cell-derived exosomes as a nanotherapeutic agent for amelioration of inflammation-induced astrocyte alterations in mice. Theranostics, 2019, 9(20): 5956-5975.

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Application of exosomes in the diagnosis and treatment of epilepsy

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