Accumulation of amyloid-β (Aβ) is implicated in the pathogenesis and development of Alzheimer's disease (AD) and it is a prime suspect for causing neuronal loss and cognitive deficits during AD. To explore the mechanisms of Aβ-induced neurodegeneration, we used Aβ-treated primary cortical neuron culture as a cell model of AD and investigated the function of miR-137 in this process. qRT-PCR and western blot were used to examine levels of miR-137, AMPA receptors (AMPARs), p-ERK1/2, and ERK1/2. MTT assay and caspases 3 activity assay were employed to examine cell viability and apoptosis. Dual-luciferase assay was used to validate the interaction between miR-137 and ERK1/2. We found that Aβ decreased cell viability, AMPAR and miR-137 levels, but increased caspase 3 activity in a dose- and time-dependent manner. Overexpression of miR-137 suppressed the Aβ-induced neurotoxicity. MiR-137 directly bound to ERK1/2 mRNA and negatively regulated its expression. Further, overexpression of ERK1/2 blocked the effects of miR-137 mimics on Aβ-induced neurotoxicity. These results provide strong evidence that miR-137 protects neurons against Aβ-induced neurotoxicity via targeting ERK1/2.

淀粉样蛋白-β (Aβ) 的积累与阿尔茨海默病 (AD) 的发病机制和发展有关，并且它是导致 AD 期间神经元丢失和认知缺陷的主要嫌疑人。为了探索 Aβ 诱导的神经变性的机制，我们使用 Aβ 处理的原代皮质神经元培养物作为 AD 的细胞模型，并研究了 miR-137 在该过程中的功能。qRT-PCR 和蛋白质印迹用于检查 miR-137、AMPA 受体 (AMPAR)、p-ERK1/2 和 ERK1/2 的水平。采用 MTT 测定和 caspase 3 活性测定来检查细胞活力和细胞凋亡。双荧光素酶测定用于验证 miR-137 和 ERK1/2 之间的相互作用。我们发现 Aβ 降低细胞活力、AMPAR 和 miR-137 水平，但以剂量和时间依赖性方式增加 caspase 3 活性。miR-137 的过表达抑制了 Aβ 诱导的神经毒性。MiR-137 直接与 ERK1/2 mRNA 结合并负调节其表达。此外，ERK1/2 的过表达阻断了 miR-137 模拟物对 Aβ 诱导的神经毒性的影响。这些结果提供了强有力的证据，证明 miR-137 通过靶向 ERK1/2 保护神经元免受 Aβ 诱导的神经毒性。