Katsuki Takahiro, Ogi Kayako, Kinno Ayaka, Kasamatsu Shingo, Ihara Hideshi, Sumitani Hidenobu
Toyo Institute of Food Technology, 23-2-4, Minami-Hanayashiki, Kawanishi-shi 666-0026, Hyogo, Japan.
Department of Biological Chemistry, Graduate School of Science, Osaka Metropolitan University, 1-1 Gakuen-cho, Naka-ku, Sakai-shi 599-8531, Osaka, Japan.
Foods. 2024 Sep 10;13(18):2858. doi: 10.3390/foods13182858.
The number of people with dementia is increasing annually worldwide. Alzheimer's disease (AD), which accounts for the highest percentage of dementia-causing diseases, remains difficult to cure, and prevention of its onset is important. We aimed to discover new AD-preventive ingredients and investigate the inhibitory effects of ten different species of seafood digests prepared by protease treatment on β-secretase 1 (BACE1) activity. Substantial inhibition of BACE1 activity was observed in five species of seafood, and protease-digested whitebait (WPD) showed the highest inhibitory effect among the ten marine samples. We further examined the potential of WPD as an AD preventive component using a familial AD strain (5xFAD) murine model. The intraperitoneal administration of WPD for 28 days substantially decreased the insoluble amyloid β content and the expression of glial fibrillary acidic protein, a marker of astrogliosis, in the cerebral cortex of the 5xFAD mice. These results strongly suggest that WPD is a novel functional food-derived ingredient with preventive effects against AD.
全球范围内，痴呆症患者人数正逐年增加。阿尔茨海默病（AD）在导致痴呆症的疾病中占比最高，仍然难以治愈，因此预防其发病至关重要。我们旨在发现新的预防AD的成分，并研究通过蛋白酶处理制备的十种不同种类的海鲜消化物对β-分泌酶1（BACE1）活性的抑制作用。在五种海鲜中观察到对BACE1活性有显著抑制作用，并且蛋白酶消化的银鱼（WPD）在十个海洋样本中显示出最高的抑制效果。我们使用家族性AD品系（5xFAD）小鼠模型进一步研究了WPD作为预防AD成分的潜力。对5xFAD小鼠腹腔注射WPD 28天，可显著降低其大脑皮层中不溶性淀粉样β蛋白含量以及星形胶质细胞增生标志物胶质纤维酸性蛋白的表达。这些结果有力地表明，WPD是一种对AD具有预防作用的新型功能性食品衍生成分。
