Brain-targeted heptapeptide-loaded exosomes attenuated ischemia–reperfusion injury by promoting the transfer of healthy mitochondria from astrocytes to neurons

BACKGROUND: The exchange of mitochondria reportedly plays an important role in cell–cell communication in the central nervous system (CNS). The transfer of fragmented and dysfunctional astrocytic mitochondria into neurons and subsequent mitochondrial fusion often cause serious neuronal damage and ce...

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Autores principales: Liu, Wei, Su, Chang, Qi, Yao, Liang, Jia, Zhao, Liang, Shi, Yijie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125840/
https://www.ncbi.nlm.nih.gov/pubmed/35606779
http://dx.doi.org/10.1186/s12951-022-01425-6
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author Liu, Wei
Su, Chang
Qi, Yao
Liang, Jia
Zhao, Liang
Shi, Yijie
author_facet Liu, Wei
Su, Chang
Qi, Yao
Liang, Jia
Zhao, Liang
Shi, Yijie
author_sort Liu, Wei
collection PubMed
description BACKGROUND: The exchange of mitochondria reportedly plays an important role in cell–cell communication in the central nervous system (CNS). The transfer of fragmented and dysfunctional astrocytic mitochondria into neurons and subsequent mitochondrial fusion often cause serious neuronal damage and cerebral ischaemic injury. METHODS: In this study, we prepared macrophage-derived exosomes laden with heptapeptide (Hep) as a dynamin-related protein-1 (Drp1)–fission 1 (Fis1) peptide inhibitor P110 to alleviate cerebral ischemia–reperfusion injury by reducing mitochondrial Drp1/Fis1 interaction-mediated astrocytic mitochondrial disorder and promoting the transfer of astrocyte-derived healthy mitochondria into neurons. RESULTS: The results demonstrated that Hep-loaded macrophage-derived exosomes (EXO-Hep) reduced mitochondrial damage in astrocytes by inhibiting the Drp1/Fis1 interaction after ischemia–reperfusion, ensuring the release of heathy astrocytic mitochondria and their subsequent transmission to neurons, alleviating mitochondria-mediated neuronal damage. CONCLUSION: EXO-Hep significantly mitigated ischemic injury in a model of transient middle cerebral artery occlusion (tMCAO) by reducing the infarct area and improving neurological performance during the process of cerebral ischemia–reperfusion. GRAPHICAL ABSTRACT: [Image: see text]
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spelling pubmed-91258402022-05-24 Brain-targeted heptapeptide-loaded exosomes attenuated ischemia–reperfusion injury by promoting the transfer of healthy mitochondria from astrocytes to neurons Liu, Wei Su, Chang Qi, Yao Liang, Jia Zhao, Liang Shi, Yijie J Nanobiotechnology Research BACKGROUND: The exchange of mitochondria reportedly plays an important role in cell–cell communication in the central nervous system (CNS). The transfer of fragmented and dysfunctional astrocytic mitochondria into neurons and subsequent mitochondrial fusion often cause serious neuronal damage and cerebral ischaemic injury. METHODS: In this study, we prepared macrophage-derived exosomes laden with heptapeptide (Hep) as a dynamin-related protein-1 (Drp1)–fission 1 (Fis1) peptide inhibitor P110 to alleviate cerebral ischemia–reperfusion injury by reducing mitochondrial Drp1/Fis1 interaction-mediated astrocytic mitochondrial disorder and promoting the transfer of astrocyte-derived healthy mitochondria into neurons. RESULTS: The results demonstrated that Hep-loaded macrophage-derived exosomes (EXO-Hep) reduced mitochondrial damage in astrocytes by inhibiting the Drp1/Fis1 interaction after ischemia–reperfusion, ensuring the release of heathy astrocytic mitochondria and their subsequent transmission to neurons, alleviating mitochondria-mediated neuronal damage. CONCLUSION: EXO-Hep significantly mitigated ischemic injury in a model of transient middle cerebral artery occlusion (tMCAO) by reducing the infarct area and improving neurological performance during the process of cerebral ischemia–reperfusion. GRAPHICAL ABSTRACT: [Image: see text] BioMed Central 2022-05-23 /pmc/articles/PMC9125840/ /pubmed/35606779 http://dx.doi.org/10.1186/s12951-022-01425-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liu, Wei
Su, Chang
Qi, Yao
Liang, Jia
Zhao, Liang
Shi, Yijie
Brain-targeted heptapeptide-loaded exosomes attenuated ischemia–reperfusion injury by promoting the transfer of healthy mitochondria from astrocytes to neurons
title Brain-targeted heptapeptide-loaded exosomes attenuated ischemia–reperfusion injury by promoting the transfer of healthy mitochondria from astrocytes to neurons
title_full Brain-targeted heptapeptide-loaded exosomes attenuated ischemia–reperfusion injury by promoting the transfer of healthy mitochondria from astrocytes to neurons
title_fullStr Brain-targeted heptapeptide-loaded exosomes attenuated ischemia–reperfusion injury by promoting the transfer of healthy mitochondria from astrocytes to neurons
title_full_unstemmed Brain-targeted heptapeptide-loaded exosomes attenuated ischemia–reperfusion injury by promoting the transfer of healthy mitochondria from astrocytes to neurons
title_short Brain-targeted heptapeptide-loaded exosomes attenuated ischemia–reperfusion injury by promoting the transfer of healthy mitochondria from astrocytes to neurons
title_sort brain-targeted heptapeptide-loaded exosomes attenuated ischemia–reperfusion injury by promoting the transfer of healthy mitochondria from astrocytes to neurons
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125840/
https://www.ncbi.nlm.nih.gov/pubmed/35606779
http://dx.doi.org/10.1186/s12951-022-01425-6
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