New Strategy for Reducing Tau Aggregation Cytologically by A Hairpinlike Molecular Inhibitor, Tannic Acid Encapsulated in Liposome
New Strategy for Reducing Tau Aggregation Cytologically by A Hairpinlike Molecular Inhibitor, Tannic Acid Encapsulated in Liposome
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通过脂质体封装的发夹状分子抑制剂单宁酸在细胞学上减少 Tau 聚集的新策略
DOI：
10.1021/acschemneuro.0c00508
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发表时间：
2020-11-04
影响因子：
5
通讯作者：
Yao, Tianming
中科院分区：
文献类型：
--
作者：
Hu, Yuan;Hu, Xiaochun;Yao, Tianming
Tau蛋白聚集的抑制是阿尔茨海默病的有吸引力的治疗靶点。然而，由于对抑制机制和药物传递动力学的认识不深，大多数抑制剂在临床试验中失败。设计策略的创新已成为当务之急。为了得到一种发夹状的分子抑制剂，我们引入了单宁酸，一种多分支的多酚分子，和它的部分，没食子酸。我们发现，单宁酸可以有效地抑制Tau聚集通过多齿螯合模式。然后，我们通过卵磷脂/β-谷甾醇将鞣酸包封在非神经毒性脂质体中，用吐温80包覆。使用transwell装置，我们在细胞学上证明单宁酸脂质体可以成功地穿过由小鼠脑微血管内皮细胞bEnd. 3组成的血脑屏障模型，并有效地减少人神经母细胞瘤细胞SK-N-SH中Tau肽R3的纤维诱导的Tau聚集。结果提示单宁酸脂质体对阿尔茨海默病有潜在的治疗作用。
Inhibition of Tau protein aggregation is an attractive therapeutic target for Alzheimer's disease. However, most of the inhibitors have failed in clinical trials due to the superficial understanding of inhibition mechanism and drug-transfer pharmacokinetics. Innovation of design strategy has become a top priority. To afford a hairpinlike molecular inhibitor, we introduced tannic acid, a multibranched polyphenol molecule, and its moiety, gallic acid. We showed that tannic acid could effectively inhibit Tau aggregation through a multidentate chelation mode. We then encapsulated tannic acid in a non-neurotoxic liposome by lecithin/beta-sitosterol, overcoating with Tween 80. Using transwell devices, we cytologically demonstrated that tannic acid liposome can successfully be transferred across the model of a blood-brain barrier made up of mouse brain microvascular endothelial cell bEnd.3 and effectively reduce Tau aggregation induced by fibrils of Tau peptide R3 in human neuroblastoma cell SK-N-SH. This result indicates the potential therapeutic effect of tannic acid liposome on Alzheimer's disease.