Alzheimer’s disease (AD) is the most common type of dementia. AD is pathologically characterized by synaptic dysfunction and cognitive decline due to the aggregation of a large amount of amyloid-β (Aβ) protein in the brain. However, recent studies have discovered that the Aβ is produced as an antimicrobial peptide that acts against bacteria and viruses. This has renewed interest in the effect of Aβ on AD. Thus, in this study, we investigated the different concentrations of Aβ on neuroprotection and further explore the related mechanisms. Firstly, we detected the cognitive function using the Y-maze test, novel object recognition memory task and Morris water maze test. Then, we analyzed the ultrastructure of synapses and mitochondria, in addition to evaluating SOD levels. We also examined the effect of Aβ on the viability and structure of the primary neurons. The western blot analysis was used to measure the protein levels. The results showed that mice treated with high concentration of Aβ impaired the learning-memory ability and disordered the structure of neurons and mitochondria. Meanwhile, high concentration of Aβ decreased the SIRT1/Nrf2 related antioxidant capacity and induced apoptosis. In contrast, mice treated with low concentration of Aβ increased SOD levels and SIRT1/Nrf2 expressions, and induced autophagy. Our data suggest that low concentration of Aβ may increase SOD levels through SIRT1/Nrf2 and induce autophagy.

中文翻译：

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淀粉样蛋白-β (25–35) 通过 SIRT1/Nrf2 调节小鼠皮质中的神经元损伤和记忆丧失


阿尔茨海默病（AD）是最常见的痴呆症类型。 AD的病理特征是大脑中大量β淀粉样蛋白（Aβ）聚集导致突触功能障碍和认知能力下降。然而，最近的研究发现，Aβ 是作为一种抗菌肽产生的，可以对抗细菌和病毒。这重新引起了人们对 Aβ 对 AD 影响的兴趣。因此，在本研究中，我们研究了不同浓度的Aβ对神经保护的作用，并进一步探讨了相关机制。首先，我们使用Y迷宫测试、新物体识别记忆任务和Morris水迷宫测试来检测认知功能。然后，除了评估 SOD 水平外，我们还分析了突触和线粒体的超微结构。我们还研究了 Aβ 对初级神经元活力和结构的影响。使用蛋白质印迹分析来测量蛋白质水平。结果表明，接受高浓度Aβ治疗的小鼠学习记忆能力受损，神经元和线粒体结构紊乱。同时，高浓度的Aβ降低了SIRT1/Nrf2相关的抗氧化能力并诱导细胞凋亡。相反，用低浓度 Aβ 处理的小鼠会增加 SOD 水平和 SIRT1/Nrf2 表达，并诱导自噬。我们的数据表明，低浓度的 Aβ 可能通过 SIRT1/Nrf2 增加 SOD 水平并诱导自噬。