Li Xixi, Ichiba Yuka, Watanabe Takuya, Yoshino Atsuko, Cheng Lihong, Nagasato Yuki, Takata Fuyuko, Dohgu Shinya, Iwasaki Katsunori, Tanaka Mitsuru, Matsui Toshiro
Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University, Fukuoka, Japan.
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
NPJ Sci Food. 2024 Dec 29;8(1):114. doi: 10.1038/s41538-024-00360-0.
In a series of studies on blood-brain barrier transportable peptides, a soybean dipeptide, Tyr-Pro, penetrated the mouse brain parenchyma after oral intake and improved short and long memory impairment in acute Alzheimer's model mice. Here, we aimed to clarify the anti-dementia effects of this peptide administered to SAMP8 mice prior to dementia onset. At the end of the 25-week protocol in 16-week-old SAMP8 mice, Tyr-Pro (10 mg/kg/day) significantly improved the reduced spatial learning ability compared with that in the control and amino acid (Tyr + Pro) groups as indicated by the results of Morris water maze tests conducted for five consecutive days. The hippocampus and cortex regions of SAMP8 harvested after the test showed lower amyloid ß (Aß) accumulation in the Tyr-Pro group than those in the control and amino acid groups. Consistent with the lower level of Aß, decreased expression of ß-secretase (BACE1) and markedly increased expression (4-times higher) of insulin degrading enzyme (IDE) were obtained compared to those in the control group. Collectively, we demonstrated that long-term daily intake of the dipeptide Tyr-Pro in SAMP8 mice may be sufficient for maintaining cognitive ability by preventing excess Aß accumulation through downregulated BACE1 and particularly upregulated IDE.
在一系列关于血脑屏障可转运肽的研究中，一种大豆二肽Tyr-Pro在口服后可穿透小鼠脑实质，并改善急性阿尔茨海默病模型小鼠的短期和长期记忆障碍。在此，我们旨在阐明在痴呆症发作前给予SAMP8小鼠这种肽的抗痴呆作用。在16周龄的SAMP8小鼠进行25周实验方案结束时，连续五天进行的莫里斯水迷宫测试结果表明，与对照组和氨基酸（Tyr + Pro）组相比，Tyr-Pro（10毫克/千克/天）显著改善了空间学习能力下降的情况。测试后收获的SAMP8小鼠的海马体和皮质区域显示，Tyr-Pro组的淀粉样β（Aβ）积累低于对照组和氨基酸组。与较低水平的Aβ一致，与对照组相比，β-分泌酶（BACE1）的表达降低，胰岛素降解酶（IDE）的表达显著增加（高出4倍）。总体而言，我们证明，在SAMP8小鼠中长期每日摄入二肽Tyr-Pro可能足以通过下调BACE1特别是上调IDE来防止过量Aβ积累，从而维持认知能力。
