Exosome: a novel neurotransmission modulator or non-canonical neurotransmitter?

Review Ageing Res Rev . 2022 Jan 3;101558. doi: 10.1016/j.arr.2021.101558. Online ahead of print. Affiliations Expand Affiliations 1 Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200072, China; Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200434, China. Electronic address: xiaohuan_xia1@163.com. 2 Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200072, China; Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200434, China. Electronic address: windyyiwang@foxmail.com. 3 Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200072, China. Electronic address: qinying@tongji.edu.cn. 4 Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200072, China. Electronic address: kasumi-box@163.com. 5 Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200072, China; Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200434, China; Collaborative Innovation Center for Brain Science, Tongji University, Shanghai 200092, China. Electronic address: jialinzheng@tongji.edu.cn. Item in Clipboard Review Xiaohuan Xia et al. Ageing Res Rev. 2022. Show details Display options Display options Format Ageing Res Rev . 2022 Jan 3;101558. doi: 10.1016/j.arr.2021.101558. Online ahead of print. Affiliations 1 Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200072, China; Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200434, China. Electronic address: xiaohuan_xia1@163.com. 2 Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200072, China; Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200434, China. Electronic address: windyyiwang@foxmail.com. 3 Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200072, China. Electronic address: qinying@tongji.edu.cn. 4 Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200072, China. Electronic address: kasumi-box@163.com. 5 Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200072, China; Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200434, China; Collaborative Innovation Center for Brain Science, Tongji University, Shanghai 200092, China. Electronic address: jialinzheng@tongji.edu.cn. Item in Clipboard CiteDisplay options Display options Format Abstract Neurotransmission is the electrical impulse-triggered propagation of signals between neurons or between neurons and other cell types such as skeletal muscle cells. Recent studies point out the involvement of exosomes, a type of small bilipid layer-enclosed extracellular vesicles, in regulating neurotransmission. Through horizontally transferring proteins, lipids, and nucleic acids, exosomes can modulate synaptic activities rapidly by controlling neurotransmitter release or progressively by regulating neural plasticity including synapse formation, neurite growth & removal, and axon guidance & elongation. In this review, we summarize the similarities and differences between exosomes and synaptic vesicles in their biogenesis, contents, and release. We also highlight the recent progress made in demonstrating the biological roles of exosome in regulating neurotransmission, and propose a modified model of neurotransmission, in which exosomes act as novel neurotransmitters. Lastly, we provide a comprehensive discussion of the enlightenment of the current knowledge on neurotransmission to the future direction of exosome research. Keywords: Central nervous system; Exosome; Extracellular vesicle; Neurotransmission; Neurotransmitter; Synaptic vesicle. Copyright © 2022. Published by Elsevier B.V. Conflict of interest statement Conflict of interests The authors declare no conflict of interests regarding the publication of this paper. Similar articles Synaptic vesicle pool-specific modification of neurotransmitter release by intravesicular free radical generation. Afuwape OA, Wasser CR, Schikorski T, Kavalali ET. Afuwape OA, et al. J Physiol. 2017 Feb 15;595(4):1223-1238. doi: 10.1113/JP273115. Epub 2016 Dec 2. J Physiol. 2017. PMID: 27723113 Free PMC article. TRP Channel Trafficking. Planells-Cases R, Ferrer-Montiel A. Planells-Cases R, et al. In: Liedtke WB, Heller S, editors. TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades. Boca Raton (FL): CRC Press/Taylor & Francis; 2007. Chapter 23. In: Liedtke WB, Heller S, editors. TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades. Boca Raton (FL): CRC Press/Taylor & Francis; 2007. Chapter 23. PMID: 21204515 Free Books & Documents. Review. The exosome journey: from biogenesis to uptake and intracellular signalling. Gurung S, Perocheau D, Touramanidou L, Baruteau J. Gurung S, et al. Cell Commun Signal. 2021 Apr 23;19(1):47. doi: 10.1186/s12964-021-00730-1. Cell Commun Signal. 2021. PMID: 33892745 Free PMC article. Review. Challenges and opportunities in exosome research-Perspectives from biology, engineering, and cancer therapy. 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