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The Combined Therapy of Berberine Treatment with lncRNA BACE1-AS Depletion Attenuates Aβ25–35 Induced Neuronal Injury Through Regulating the Expression of miR-132-3p in Neuronal Cells

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Abstract

Accumulating articles reported that berberine (Ber) played a neuroprotective role in Alzheimer’s disease (AD). Long noncoding RNAs (lncRNAs) have been identified as biomarkers and therapeutic targets of AD. However, the precise mechanism by which lncRNA β-amyloid cleaving enzyme 1 antisense RNA (BACE1-AS)regulates the progression of AD remains largely unknown. HPN and SK-N-SH cells treated with amyloid β 25–35 (Aβ25–35) were regarded as AD model in vitro. Cell survival rate was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Lactate dehydrogenase (LDH) cytotoxicity assay was conducted to detect the cytotoxicity of neuronal cells. Flow cytometry was performed to determine the intracellular concentration of Ca2+, reactive oxygen species (ROS) and apoptosis of neuronal cells. Western blot assay was carried out to detect the apoptosis-related proteins of neuronal cells. The abundance of lncRNA BACE1-AS and miR-132-3p was measured by quantitative real time polymerase chain reaction (qRT-PCR). The binding sites between miR-132-3p and BACE1-AS were predicted by Starbase, and the combination was confirmed by dual-luciferase reporter assay. We found that Ber alleviated Aβ25–35 induced neuronal injury in AD model, especially in high concentration Ber group. The enrichment of BACE1-AS was positively regulated by Aβ25–35 and was inversely modulated by Ber in neuronal cells. The interference of BACE1-AS alleviated the neuronal damage of AD model. miR-132-3p was a direct target of lncRNA BACE1-AS in HEK293T cells, and it was negatively regulated by BACE1-AS in neuronal cells. BACE1-AS accumulation reversed the protective effect of miR-132-3p overexpression on AD model. Ber treatment and BACE1-AS intervention recovered the viability of AD model. Ber up-regulated the level of miR-132-3p via BACE1-AS in SK-N-SH and HPN neuronal cells. in conclucsion, Ber protected neuronal cells against Aβ25–35 at least partly through BACE1-AS/miR-132-3p axis. The combined therapy of Ber treatment with BACE1-AS depletion might provide new insight into AD treatment.

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Funding

This work was supported by the Science and Technology Office of Henan Province (scientific and technological project) (Grant Number: 162102310289) and Science and Technology Office of Henan Province (international program) (Grant Number: 124300510017).

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Authors and Affiliations

  1. Department of Neurology, Henan Provincial People’s Hospital, No. 7 Weiwu Road, Zhengzhou, 451450, China

    Yunli Ge, Xiaolin Song, Jianfeng Liu, Chun Liu & Changshui Xu

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  1. Yunli Ge
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  2. Xiaolin Song
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  3. Jianfeng Liu
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  4. Chun Liu
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Correspondence to Yunli Ge or Changshui Xu.

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Ge, Y., Song, X., Liu, J. et al. The Combined Therapy of Berberine Treatment with lncRNA BACE1-AS Depletion Attenuates Aβ25–35 Induced Neuronal Injury Through Regulating the Expression of miR-132-3p in Neuronal Cells. Neurochem Res 45, 741–751 (2020). https://doi.org/10.1007/s11064-019-02947-6

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  • DOI: https://doi.org/10.1007/s11064-019-02947-6

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