Alzheimer'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 Aβ_1-42-treated SH-SY5Y cells. Autophagy activity was increased in both Tg mice and Aβ_1-42-treated cells. BACE1-AS knockdown alleviated Aβ_1-42-induced cell injury. Rapamycin abolished the protective effects of sh BACE1-AS against Aβ_1-42 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 Aβ_1-42-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.

阿尔茨海默氏病（AD）是最常见的神经退行性疾病，其特征是进行性记忆丧失和认知功能障碍。长的非编码RNA（lncRNA）已被证明是AD最有希望的生物标志物和治疗靶标之一。在这里，我们旨在调查lncRNA BACE1-AS是否在AD的潜在机制中发挥作用。使用qRT-PCR检测BACE1-AS，miR-214-3p和ATG5 mRNA的表达。使用蛋白质印迹分析检查了LC3，P62，ATG5，Bcl-2，p-Tau和裂解的胱天蛋白酶3蛋白的表达。分别使用流式细胞仪，LDH试剂盒和DCFH-DA分析评估细胞凋亡，细胞毒性和ROS水平。BACE1-AS或ATG5与miR-214-3p之间的相互作用已通过双重萤光素酶报告基因检测方法进行了验证。HE染色和TUNEL测定法用于评估海马神经元损伤。发现AD患者的血清样品，AD转基因（Tg）小鼠的脑组织和Aβ中的BACE1-AS水平上调_1-42处理的SH-SY5Y细胞。在Tg小鼠和_Aβ1-42处理的细胞中，自噬活性均增加。BACE1-AS抑制可减轻_Aβ1-42诱导的细胞损伤。雷帕霉素取消了sh BACE1-AS对_Aβ1-42诱导的细胞损伤的保护作用。BACE1-AS通过结合miR-214-3p间接调节ATG5的表达。miR-214-3p抑制剂逆转了sh BACE1-AS和sh ATG5对_Aβ1-42诱导的细胞损伤的保护作用。抑制BACE1-AS通过抑制体内自噬减轻神经元损伤。我们的发现表明，通过在AD中通过miR-214-3p / ATG5信号轴调节自噬，BACE1-AS的沉默可以减轻神经元损伤。