Deposition of an amyloid-β peptide is one of the first events in the pathophysiology of Alzheimer’s disease (AD) and is clinically characterized by Aβ plaques, tau tangles, and behavioral impairments that lead to neuronal death. A substantial number of studies encourage targeting the skewness in the production and degradation of amyloid-β could be among the promising therapies in the disease. Neuronal autophagy has emerged for an essential role in the degradation of such toxic aggregate-prone proteins in various neurodegenerative diseases. We profiled a small library of common dietary compounds and identified those that can enhance autophagy in neuronal cells. Here we noted naringenin in silico exhibits a robust affinity with AMP-activated protein kinase (AMPK) and upregulated AMPK-mediated autophagy signaling in neurons. Naringenin can induce autophagy promoting proteins such as ULK1, Beclin1, ATG5, and ATG7 in Neuro2a cells and primary mouse neurons as well. The knockdown of AMPK by siRNA-AMPK was complemented by naringenin that restored transcript levels of AMPK. Further, naringenin can reduce the levels of Aβ at a nontoxic concentration from neuronal cells. Moreover, it maintained the mitochondrial membrane potential and resisted reactive oxygen species production, which led to the protection against Aβ_1–42 evoked neurotoxicity. This highlights the neuroprotective potential of naringenin that can be developed as an anti-amyloidogenic nutraceutical.

淀粉样蛋白-β 肽的沉积是阿尔茨海默病 (AD) 病理生理学中的第一个事件之一，其临床特征是 Aβ 斑块、tau 缠结和导致神经元死亡的行为障碍。大量研究鼓励针对β-淀粉样蛋白的产生和降解的偏度可能是该疾病的有希望的疗法之一。神经元自噬在各种神经退行性疾病中这种有毒的易聚集蛋白的降解中发挥了重要作用。我们分析了一个小型的常见膳食化合物库，并确定了那些可以增强神经元细胞自噬的化合物。在这里，我们注意到计算机中的柚皮素与 AMP 活化蛋白激酶 (AMPK) 表现出强烈的亲和力，并在神经元中上调了 AMPK 介导的自噬信号传导。Naringenin 可以在 Neuro2a 细胞和原代小鼠神经元中诱导自噬促进蛋白，例如 ULK1、Beclin1、ATG5 和 ATG7。siRNA-AMPK 对 AMPK 的敲低由恢复 AMPK 转录水平的柚皮素补充。此外，柚皮素可以降低来自神经元细胞的无毒浓度的 Aβ 水平。此外，它维持线粒体膜电位并抵抗活性氧物质的产生，从而导致对 Aβ 的保护_1-42诱发神经毒性。这突出了柚皮素的神经保护潜力，可以开发为一种抗淀粉样蛋白营养保健品。