微泡
神经保护
药理学
细胞周期蛋白依赖激酶5
认知功能衰退
生物利用度
药物输送
神经科学
药品
医学
激酶
疾病
化学
生物
蛋白激酶A
内科学
痴呆
小RNA
生物化学
有机化学
基因
丝裂原活化蛋白激酶激酶
作者
Qi Yao,Lin Guo,Yibin Jiang,Yijie Shi,Hai-juan Sui,Liang Zhao
出处
期刊:Drug Delivery
[Informa]
日期:2020-01-01
卷期号:27 (1): 745-755
被引量:141
标识
DOI:10.1080/10717544.2020.1762262
摘要
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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