Chlorogenic Acid Alleviates Aβ25-35-Induced Autophagy and Cognitive Impairment via the mTOR/TFEB Signaling Pathway
Chlorogenic Acid Alleviates Aβ25-35-Induced Autophagy and Cognitive Impairment via the mTOR/TFEB Signaling Pathway
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DOI：
10.2147/dddt.s235969
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发表时间：
2020-01-01
影响因子：
4.8
通讯作者：
Xu, Shijun
中科院分区：
文献类型：
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作者：
Gao, Lijuan;Li, Xiaoqiong;Xu, Shijun
目的：绿原酸(CGA)是一种从水果和蔬菜中分离出来的酚酸，已被证实与阿尔茨海默病(AD)有关，具有神经保护作用。然而，CGA预防AD认知障碍的确切机制还没有得到很好的研究。本研究旨在利用Aβ(25)(-)(35)诱导的APP/PS1小鼠SH-SY5Y神经元损伤和认知缺陷模型，探讨CGA作用的分子机制。方法：采用3月龄雄性APP/PS1双转基因小鼠和人神经母细胞瘤细胞系SH-SY5Y，分别在体内和体外评价CGA对AD的影响。用Morris水迷宫(MWM)测试小鼠的认知功能。采用苏木精-伊红染色、单丹西林荧光染色、溶血追踪剂红(LTR)染色和免疫荧光染色等方法评价细胞的形态变化。免疫印迹分析自噬标志物(LC3B-II/LC3B-I、p62/SQSTM、BELINL和ATG5)和溶酶体功能相关标志物(组织蛋白D、mTOR、p-mTOR p70S6K、p-p70S6K和TFEB)的蛋白表达。结果：CGA可明显改善APP/PS1小鼠的空间记忆，减轻神经元损伤，抑制自噬(P
Purpose: Chlorogenic acid (CGA), a phenolic acid isolated from fruits and vegetables, has been established to have neuroprotective properties in relation to Alzheimer's disease (AD). However, the precise mechanism by which CGA prevents cognitive deficits in AD has not been well studied. This study aimed to explore the potential molecular mechanism of CGA action using an A beta(25)(-)(35) induced SH-SY5Y neuron injury and cogxnitive deficits model in APP/PS1 mice.Methods: Three-month-old male APP/PS1 double transgenic mice and a human neuroblastoma cell line (SH-SY5Y) were used to assess the effects of CGA on AD in vivo and in vitro, respectively. Cognitive function in mice was measured using a Morris water maze (MWM) test. Hematoxylin and eosin, monodansylcadaverine fluorescence, LysoTracker Red (LTR), and immunofluorescence staining were used to evaluate the morphological changes in vivo and in vitro. The protein expressions of autophagy markers (LC3B-II/LC3B-I, p62/SQSTM, beclinl and Atg5) and lysosomal-function-related markers (cathepsin D, mTOR, p-mTOR P70S6K, p-p70s6k and TFEB) were analyzed with Western blot analyses.Results: CGA treatment significantly improved spatial memory, relieved neuron damage, and inhibited autophagy in APP/PS1 mice (P