血脑屏障
封堵器
基质金属蛋白酶
污渍
紧密连接
化学
细胞生物学
海马体
生物
生物化学
神经科学
中枢神经系统
基因
作者
Qiao Dang,Dan Wu,Yanru Li,Fang Li,Chunlei Liu,Xiyan Wang,Xiaoting Liu,Weihong Min
标识
DOI:10.1016/j.foodres.2022.112029
摘要
Disruption of the blood-brain barrier (BBB) has been observed in several neurological diseases. This study explored the protective effect of the walnut-derived peptide TWLPLPR (TW-7) against d-galactose (d-gal)-induced cognitive disturbance in mice and its potential protection mechanism in β-amyloid 25-35 (Aβ25-35)-injured bEnd.3 cells. TW-7 improved the learning ability and memory of the cognitive impairment mice. Transmission electron microscopy showed that the BBB integrity in the hippocampus was restored; while immunofluorescence analysis and western blotting indicated that the protection of BBB integrity was associated with increased expression levels of tight junction (TJ) proteins. In Aβ25-35-damaged bEnd.3 cells, treatment with a matrix metalloproteinase 9 (MMP-9) activator and inhibitor confirmed that TW-7 partially reduced MMP-9 expression and increased zonula occludin-1 (ZO-1) and Claudin-5 expression. Furthermore, TW-7 reduced MMP-9 levels by forming stable complexes with it and by inhibiting the NF-κB p65/iNos pathway. These data suggested that TW-7 maintains BBB integrity by inhibiting the expression and activity of MMP-9, and TW-7 improves learning and memory ability in mice.
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