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Brain delivery of quercetin-loaded exosomes improved cognitive function in AD mice by inhibiting phosphorylated tau-mediated neurofibrillary tangles

It is reported that quercetin (Que) can prevent tau pathology and induce neuroprotection by improving cognitive and functional symptoms in the treatment of Alzheimer’s disease (AD). However, its clinical application has been limited due to its poor brain targeting and bioavailability. Exosomes are c...

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Autores principales: Qi, Yao, Guo, Lin, Jiang, Yibing, Shi, Yijie, Sui, Haijuan, Zhao, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269046/
https://www.ncbi.nlm.nih.gov/pubmed/32397764
http://dx.doi.org/10.1080/10717544.2020.1762262
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author Qi, Yao
Guo, Lin
Jiang, Yibing
Shi, Yijie
Sui, Haijuan
Zhao, Liang
author_facet Qi, Yao
Guo, Lin
Jiang, Yibing
Shi, Yijie
Sui, Haijuan
Zhao, Liang
author_sort Qi, Yao
collection PubMed
description It is reported that quercetin (Que) can prevent tau pathology and induce neuroprotection by improving cognitive and functional symptoms in the treatment of Alzheimer’s disease (AD). However, its clinical application has been limited due to its poor brain targeting and bioavailability. Exosomes are considered as cargo carriers for intercellular communication and especially serve as a natural and important drug brain delivery platform for achieving better treatment of central neurological diseases. Here, we developed plasma exosomes (Exo) loaded with Que (Exo-Que) to improve the drug bioavailability, enhance the brain targeting of Que and potently ameliorate cognitive dysfunction in okadaic acid (OA)-induced AD mice. Our results showed that Exo-Que improved brain targeting of Que as well as significantly enhanced bioavailability of Que. Furthermore, compared with free Que, Exo-Que better relieved the symptoms of AD by inhibiting cyclin-dependent kinase 5 (CDK5)-mediated phosphorylation of Tau and reducing formation of insoluble neurofibrillary tangles (NFTs), suggesting its therapeutic potential for better treatment of AD.
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spelling pubmed-72690462020-06-11 Brain delivery of quercetin-loaded exosomes improved cognitive function in AD mice by inhibiting phosphorylated tau-mediated neurofibrillary tangles Qi, Yao Guo, Lin Jiang, Yibing Shi, Yijie Sui, Haijuan Zhao, Liang Drug Deliv Research Article It is reported that quercetin (Que) can prevent tau pathology and induce neuroprotection by improving cognitive and functional symptoms in the treatment of Alzheimer’s disease (AD). However, its clinical application has been limited due to its poor brain targeting and bioavailability. Exosomes are considered as cargo carriers for intercellular communication and especially serve as a natural and important drug brain delivery platform for achieving better treatment of central neurological diseases. Here, we developed plasma exosomes (Exo) loaded with Que (Exo-Que) to improve the drug bioavailability, enhance the brain targeting of Que and potently ameliorate cognitive dysfunction in okadaic acid (OA)-induced AD mice. Our results showed that Exo-Que improved brain targeting of Que as well as significantly enhanced bioavailability of Que. Furthermore, compared with free Que, Exo-Que better relieved the symptoms of AD by inhibiting cyclin-dependent kinase 5 (CDK5)-mediated phosphorylation of Tau and reducing formation of insoluble neurofibrillary tangles (NFTs), suggesting its therapeutic potential for better treatment of AD. Taylor & Francis 2020-05-13 /pmc/articles/PMC7269046/ /pubmed/32397764 http://dx.doi.org/10.1080/10717544.2020.1762262 Text en © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Qi, Yao
Guo, Lin
Jiang, Yibing
Shi, Yijie
Sui, Haijuan
Zhao, Liang
Brain delivery of quercetin-loaded exosomes improved cognitive function in AD mice by inhibiting phosphorylated tau-mediated neurofibrillary tangles
title Brain delivery of quercetin-loaded exosomes improved cognitive function in AD mice by inhibiting phosphorylated tau-mediated neurofibrillary tangles
title_full Brain delivery of quercetin-loaded exosomes improved cognitive function in AD mice by inhibiting phosphorylated tau-mediated neurofibrillary tangles
title_fullStr Brain delivery of quercetin-loaded exosomes improved cognitive function in AD mice by inhibiting phosphorylated tau-mediated neurofibrillary tangles
title_full_unstemmed Brain delivery of quercetin-loaded exosomes improved cognitive function in AD mice by inhibiting phosphorylated tau-mediated neurofibrillary tangles
title_short Brain delivery of quercetin-loaded exosomes improved cognitive function in AD mice by inhibiting phosphorylated tau-mediated neurofibrillary tangles
title_sort brain delivery of quercetin-loaded exosomes improved cognitive function in ad mice by inhibiting phosphorylated tau-mediated neurofibrillary tangles
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269046/
https://www.ncbi.nlm.nih.gov/pubmed/32397764
http://dx.doi.org/10.1080/10717544.2020.1762262
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