Preventive effect of Tyr-Pro, a blood-brain barrier transportable dipeptide, on memory impairment in SAMP8 mice

Abstract 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 t...

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Main Authors: Xixi Li, Yuka Ichiba, Takuya Watanabe, Atsuko Yoshino, Lihong Cheng, Yuki Nagasato, Fuyuko Takata, Shinya Dohgu, Katsunori Iwasaki, Mitsuru Tanaka, Toshiro Matsui
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:npj Science of Food
Online Access:https://doi.org/10.1038/s41538-024-00360-0
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Summary:Abstract 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.
ISSN:2396-8370