Alzheimer’s disease (AD) is considered a prevalent neurological disorder with a neurodegenerative nature in elderly people. Oxidative stress and neuroinflammation due to amyloid β (Aβ) peptides are strongly involved in AD pathogenesis. Klotho is an anti-aging protein with multiple protective effects that its deficiency is involved in development of age-related disorders. In this study, we investigated the beneficial effect of Klotho pretreatment at different concentrations of 0.5, 1, and 2 nM against Aβ1–42 toxicity at a concentration of 20 μM in human SH-SY5Y neuroblastoma cells. Our findings showed that Klotho could significantly and partially restore cell viability and decrease reactive oxygen species (known as ROS) and improve superoxide dismutase activity (SOD) in addition to reduction of caspase 3 activity and DNA fragmentation following Aβ1–42 challenge. In addition, exogenous Klotho also reduced inflammatory biomarkers consisting of nuclear factor-kB (NF-kB), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in Aβ-exposed cells. Besides, Klotho caused downregulation of Wnt1 level, upregulation of phosphorylated cyclic AMP response element binding (pCREB), and mRNA levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) with no significant alteration of epsilon isoform of protein kinase C (PKCε) after Aβ toxicity. In summary, Klotho could alleviate apoptosis, oxidative stress, and inflammation in human neuroblastoma cells after Aβ challenge and its beneficial effect is partially exerted through appropriate modulation of Wnt1/pCREB/Nrf2/HO-1 signaling.

阿尔茨海默病 (AD) 被认为是老年人中一种普遍存在的神经系统疾病，具有神经退行性。由淀粉样蛋白 β (Aβ) 肽引起的氧化应激和神经炎症与 AD 发病机制密切相关。Klotho 是一种具有多重保护作用的抗衰老蛋白，其缺乏与年龄相关疾病的发展有关。在本研究中，我们研究了 0.5、1 和 2 nM 不同浓度的 Klotho 预处理对人 SH-SY5Y 神经母细胞瘤细胞中 20 μM 浓度的 Aβ1-42 毒性的有益作用。我们的研究结果表明，除了降低 Aβ1-42 激发后的半胱天冬酶 3 活性和 DNA 断裂外，Klotho 还可以显着和部分恢复细胞活力，减少活性氧（称为 ROS）并提高超氧化物歧化酶活性（SOD）。此外，外源性 Klotho 还减少了 Aβ 暴露细胞中由核因子-kB (NF-kB)、白细胞介素-1β (IL-1β) 和肿瘤坏死因子-α (TNF-α) 组成的炎症生物标志物。此外，Klotho 引起 Wnt1 水平的下调、磷酸化环 AMP 反应元件结合 (pCREB) 的上调以及核因子红细胞 2 相关因子 2 (Nrf2) 和血红素加氧酶 1 (HO-1) 的 mRNA 水平，但没有显着改变Aβ 毒性后蛋白激酶 C (PKCε) 的 epsilon 异构体。总之，Klotho 可以减轻细胞凋亡，