LncRNA BACE1-AS Promotes Autophagy-Mediated Neuronal Damage Through The miR-214-3p/ATG5 Signalling Axis In Alzheimer's Disease

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 Ab1-42-treated SH-SY5Y cells. Autophagy activity was increased in both Tg mice and Ab1-42-treated cells. BACE1-AS knockdown alleviated Ab1-42-induced cell injury. Rapamycin abolished the protective effects of sh BACE1-AS against Ab1-42 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 Ab1-42-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. (c) 2020 IBRO. Published by Elsevier Ltd. All rights reserved.

Automated summary

Alzheimer's disease (AD) is characterized by progressive memory loss and cognitive dysfunction, with long non-coding RNAs (lncRNAs) showing promise as biomarkers and therapeutic targets. The study found that silencing of lncRNA BACE1-AS alleviated neuronal injury by regulating autophagy through the miR-214-3p/ATG5 signaling axis in AD. These findings suggest a potential therapeutic target for AD treatment.