Walnut-derived peptides ameliorate d-galactose-induced memory impairments in a mouse model via inhibition of MMP-9-mediated blood–brain barrier disruption. (December 2022) - Dang, Qiao
Graphical abstract: Highlights: Walnut peptides ameliorate d -galactose-induced memory impairments in a mouse model. Amelioration is due to inhibition of MMP-9-mediated blood–brain barrier disruption. TW-7 maintains BBB integrity by inhibiting the expression and activity of MMP-9. Abstract: 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 (A β 25-35 )-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 A β 25-35 -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- κ B 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.