College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, P. R. China.
College of Food and Health, Zhejiang A & F University, Hangzhou 311300, P.R. China.
Food Funct. 2024 Feb 19;15(4):2295-2313. doi: 10.1039/d3fo05076a.
NLRP3 inflammasome activation plays a key role in the development of diabetes-induced cognitive impairment. However, strategies to inhibit NLRP3 inflammasome activation remain elusive. Herein, we evaluated the impact of a walnut-derived peptide, TWLPLPR (TW-7), on cognitive impairment in high-fat diet/streptozotocin-induced type 2 diabetes mellitus (T2DM) mice and explored its underlying mechanisms in high glucose-induced HT-22 cells. In the Morris water maze test, TW-7 alleviated cognitive deficits in mice; this was confirmed at the level of synaptic structure and dendritic spine density in the mouse hippocampus using transmission electron microscopy and Golgi staining. TW-7 increased the expression of synaptic plasticity-related proteins and suppressed the NEK7/NLRP3 inflammatory pathway, as determined by western blotting and immunofluorescence analysis. The mechanism of action of TW-7 was verified in an HT-22 cell model of high glucose-induced insulin resistance. Collectively, TW-7 could regulate T2DM neuroinflammation and synaptic function-induced cognitive impairment by inhibiting NLRP3 inflammasome activation and improving synaptic plasticity.
NLRP3 炎性小体的激活在糖尿病引起的认知障碍的发展中起着关键作用。然而，抑制 NLRP3 炎性小体激活的策略仍然难以捉摸。本文研究了一种来源于核桃的肽 TW-7 对高脂肪饮食/链脲佐菌素诱导的 2 型糖尿病 (T2DM) 小鼠认知障碍的影响，并探讨了其在高糖诱导的 HT-22 细胞中潜在的作用机制。在 Morris 水迷宫测试中，TW-7 缓解了小鼠的认知缺陷；这在透射电子显微镜和高尔基染色的小鼠海马体中得到了证实，即突触结构和树突棘密度得到了改善。通过 Western blot 和免疫荧光分析，TW-7 增加了与突触可塑性相关的蛋白的表达，并抑制了 NEK7/NLRP3 炎症途径。TW-7 在高糖诱导的 HT-22 细胞胰岛素抵抗模型中的作用机制得到了验证。综上所述，TW-7 可能通过抑制 NLRP3 炎性小体激活和改善突触可塑性来调节 T2DM 神经炎症和突触功能引起的认知障碍。
