• Yuan Zhou, Yao Ge, Qi Liu, Yun-Xiao Li, Xu Chao, Jian-Jun Guan, Yong-Chang Diwu, and Qi Zhang.
• Department of Anatomy, Basic Medical College, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, PR China; Discipline Innovation Team of Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, PR China; Shaanxi Key Laboratory of Chinese Medicine Encephalopathy, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, PR China. Electronic address: 2111073@sntcm.edu.cn.
• Neuroscience. 2021 Feb 10; 455: 52-64.

AbstractAlzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by progressive memory loss and cognitive dysfunction. Long non-coding RNAs (lncRNAs) have been shown to be among the most promising biomarkers and therapeutic targets of AD. Here, we aimed to investigate whether lncRNA BACE1-AS plays a role in the potential mechanisms of AD. The expression of BACE1-AS, miR-214-3p and ATG5 mRNA was detected using qRT-PCR. The expression of the LC3, P62, ATG5, Bcl-2, p-Tau and cleaved-caspase 3 proteins was examined using western blot analysis. Cell apoptosis, cytotoxicity and ROS levels were estimated using flow cytometry, an LDH kit and a DCFH-DA assay, respectively. The interaction between BACE1-AS or ATG5 and miR-214-3p was validated using a dual-luciferase reporter assay. HE staining and a TUNEL assay were employed to evaluate hippocampal neuronal injury. The BACE1-AS level was found to be upregulated in serum samples of AD patients, brain tissues of AD transgenic (Tg) mice and Aβ1-42-treated SH-SY5Y cells. Autophagy activity was increased in both Tg mice and Aβ1-42-treated cells. BACE1-AS knockdown alleviated Aβ1-42-induced cell injury. Rapamycin abolished the protective effects of sh BACE1-AS against Aβ1-42 induced cell injury. BACE1-AS indirectly regulated ATG5 expression by binding miR-214-3p. The miR-214-3p inhibitor reversed the protective effects of sh BACE1-AS and sh ATG5 against Aβ1-42-induced cell injury. Knockdown of BACE1-AS alleviated neuronal injury by repressing autophagy in vivo. Our findings demonstrate that silencing of BACE1-AS alleviated neuronal injury by regulating autophagy through the miR-214-3p/ATG5 signalling axis in AD.Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.

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