Background

Alzheimer's disease (AD) is a common neurodegenerative disease, which is characterized by aberrant accumulation of amyloid-β (Aβ) and neuroinflammation. The purpose of this study was to explore the regulatory effects of long non-coding RNA (lncRNA) MAGI2-AS3 and microRNA-374b-5p (miR-374b-5p) on Aβ-induced neurotoxicity and neuroinflammation, as well as the relationship between MAGI2-AS3 and miR-374b-5p in AD patients.

Methods

A luciferase reporter assay was used to analyze the interaction between MAGI2-AS3 and miR-374b-5p and between miR-374b-5p and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). SH-SY5Y and BV2 cells treated with Aβ25–35 were used to mimic neuronal injury and neuroinflammation in AD pathogenesis. Cell viability was evaluated using a MTT assay, and pro-inflammatory cytokine levels were measured using ELISA kits. MAGI2-AS3 and miR-374b-5p expression was examined using quantitative real-time PCR.

Results

BACE1 served as a target gene of miR-374b-5p, and MAGI2-AS3 could sponge miR-374b-5p. The expression of MAGI2-AS3 was increased, and miR-374b-5p was decreased in both SH-SY5Y and BV2 cells exposed to Aβ25–35. MAGI2-AS3 reduction enhanced neuronal viability and attenuated neuroinflammation in AD cell models, and miR-374b-5p overexpression led to same effects, but miR-374b-5p inhibition reversed these effects. Serum MAGI2-AS3 and miR-374b-5p levels in AD patients were negatively correlated and correlated with disease severity.

Conclusion

The findings indicated that the MAGI2-AS3/miR-374b-5p axis regulates Aβ-induced neurotoxicity in SH-SY5Y cells and neuroinflammation in BV2 cells. The MAGI2-AS3/miR-374b-5p axis may provide novel biomarkers and therapeutic targets for AD.

中文翻译：

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阿尔茨海默氏病中lncRNA MAGI2-AS3的失调通过使miR-374b-5p海绵化而减弱了淀粉样β诱导的神经毒性和神经炎症

背景

阿尔茨海默氏病（AD）是一种常见的神经退行性疾病，其特征在于淀粉样β（Aβ）异常积累和神经炎症。这项研究的目的是探讨长非编码RNA（lncRNA）MAGI2-AS3和microRNA-374b-5p（miR-374b-5p）对Aβ诱导的神经毒性和神经炎症的调节作用，以及它们之间的关系。 AD患者的MAGI2-AS3和miR-374b-5p。

方法

萤光素酶报告基因分析用于分析MAGI2-AS3与miR-374b-5p之间以及miR-374b-5p与β-位淀粉样前体蛋白裂解酶1（BACE1）之间的相互作用。Aβ25-35处理的SH-SY5Y和BV2细胞被用于模拟AD发病机理中的神经元损伤和神经炎症。使用MTT分析评估细胞活力，并使用ELISA试剂盒测量促炎细胞因子水平。使用定量实时PCR检测MAGI2-AS3和miR-374b-5p的表达。

结果

BACE1作为miR-374b-5p的靶基因，MAGI2-AS3可以使miR-374b-5p脱颖而出。在暴露于Aβ25-35的SH-SY5Y和BV2细胞中，MAGI2-AS3的表达增加，而miR-374b-5p的表达减少。在AD细胞模型中，MAGI2-AS3的减少增强了神经元的活力并减轻了神经炎症，miR-374b-5p的过表达导致了相同的作用，但miR-374b-5p的抑制作用却逆转了这些作用。AD患者的血清MAGI2-AS3和miR-374b-5p水平呈负相关，并与疾病严重程度相关。

结论

这些发现表明，MAGI2-AS3 / miR-374b-5p轴可调节Aβ诱导的SH-SY5Y细胞的神经毒性和BV2细胞的神经炎症。MAGI2-AS3 / miR-374b-5p轴可能为AD提供新的生物标志物和治疗靶标。