Wu Hanshuo, Liu Rui, Zhang Xinxue, Wang Hualei, Meng Ganlu, Ren Jie, Liu Wenying, Li Shuguo
Beijing Engineering Research Center of Protein & Functional Peptides, China National Research Institute of Food and Fermentation Industries, Beijing, China.
College of Food and Biology, Hebei University of Science and Technology, Shijiazhuang, China.
J Sci Food Agric. 2025 Aug 30;105(11):5738-5750. doi: 10.1002/jsfa.14307. Epub 2025 May 15.
There are more and more Alzheimer's patients. The formation of plaques of Aβ in the brain is one of the main causes of Alzheimer's disease. Corn oligopeptides have natural antioxidant effects. It is aimed to develop functional corn oligopeptides to prevent Alzheimer's disease through antioxidation.
According to previous laboratory studies, peptides of corn oligopeptides were screened by biological activity score and ADMET prediction, and molecular docking technology was used to screen the peptides that had high binding energy with Aβ. The protective effects of the selected peptides were evaluated against oxidative stress in Aβ-injured SHSY5Y cells, and the mechanism of the effects in the protein kinase A (PKA)/cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)-mediated signaling pathway was investigated, which is closely related to neurodegenerative and neurological diseases.
The results showed that three peptides (GL, FA and FQ) significantly increased the cell viability of Aβ-induced cells and mitochondrial intensity and decreased extracellular lactate dehydrogenase content. They also improved intracellular oxidative stress caused by Aβ, including reducing the overproduction of intracellular reactive oxygen species, and increasing the content of lipid oxidation, superoxide dismutase and glutathione peroxidase. In addition, western blot showed that treatment with GL, FA and FQ significantly increased the expression of PKA, CREB and BDNF, whereas cells injured with Aβ decreased the expression of these signaling proteins.
These results suggest that peptides of corn oligopeptides can effectively improve Aβ-induced Alzheimer's disease, and may improve oxidative stress response to protective nerve cells by up-regulating the protein expression of the PKA/CREB/BDNF signaling pathway. © 2025 Society of Chemical Industry.
阿尔茨海默病患者越来越多。大脑中β淀粉样蛋白（Aβ）斑块的形成是阿尔茨海默病的主要病因之一。玉米寡肽具有天然抗氧化作用。旨在开发功能性玉米寡肽，通过抗氧化作用预防阿尔茨海默病。
根据以往的实验室研究，通过生物活性评分和ADMET预测筛选玉米寡肽的肽段，并利用分子对接技术筛选与Aβ具有高结合能的肽段。评估所选肽段对Aβ损伤的SHSY5Y细胞氧化应激的保护作用，并研究其在蛋白激酶A（PKA）/环磷酸腺苷反应元件结合蛋白（CREB）/脑源性神经营养因子（BDNF）介导的信号通路中的作用机制，该信号通路与神经退行性疾病和神经系统疾病密切相关。
结果表明，三种肽段（GL、FA和FQ）显著提高了Aβ诱导细胞的细胞活力和线粒体强度，并降低了细胞外乳酸脱氢酶含量。它们还改善了Aβ引起的细胞内氧化应激，包括减少细胞内活性氧的过量产生，以及增加脂质氧化、超氧化物歧化酶和谷胱甘肽过氧化物酶的含量。此外，蛋白质印迹法显示，用GL、FA和FQ处理显著增加了PKA、CREB和BDNF的表达，而Aβ损伤的细胞则降低了这些信号蛋白的表达。
这些结果表明，玉米寡肽的肽段可以有效改善Aβ诱导的阿尔茨海默病，并且可能通过上调PKA/CREB/BDNF信号通路的蛋白表达来改善氧化应激反应以保护神经细胞。©2025化学工业协会。
