This study investigated the anti-inflammatory effects of novel pseudotripeptides (GPE 1–3) as potential candidates to counteract neuroinflammation processes in Alzheimer’s disease.

GPE 1–3 pseudotripeptides are synthetic derivatives of Gly-l-Pro-l-Glu (GPE), the N-terminal tripeptide of IGF-1, obtained through the introduction of isosteres of the amidic bond (aminomethylene unit) to increase the metabolic stability of the native tripeptide. The results showed that all synthetic derivatives possessed higher half-lives (t_1/2 > 4 h) than GPE (t_1/2 = 30 min) in human plasma and had good water solubility. The biological results demonstrated that GPE 1–3 had protective properties in several experimental models of treated THP-1 cells. Notably, the novel pseudotripeptides influenced inflammatory cytokine expression (IL-1β, IL-18, and TNF-α) in Aβ_25–35-, PMA-, and LPS-treated THP-1 cells. In PMA-differentiated THP-1 macrophages, both GPE 1 and GPE 3 reduced the expression levels of all selected cyto-chemokines, even though GPE 3 showed the best neuroprotective properties.

本实验研究新颖pseudotripeptides的抗炎作用（GPE 1 - 3）作为可能的候选，以抵消神经炎症过程在阿尔茨海默氏病。

GPE 1 - 3个pseudotripeptides是Gly-的合成衍生物升-Pro-升-Glu（GPE），则Ñ IGF-1的末端三肽，通过引入酰胺键（氨基亚甲基单元）的电子等排体的获得增加的代谢天然三肽的稳定性。结果表明，所有合成衍生物 在人血浆中的半衰期（t _1/2  > 4 h）比GPE（t _1/2 = 30 min）高，并且具有良好的水溶性。生物结果表明，GPE 1 - 3在几种处理过的THP-1细胞的实验模型中具有保护性。值得注意的是，新颖pseudotripeptides在Aβ的影响炎性细胞因子的表达（IL-1β，IL-18和TNF-α）_25-35 - ，PMA-，和LPS处理的THP-1细胞。在PMA分化的THP-1巨噬细胞中，即使GPE 3显示出最佳的神经保护特性，GPE 1和GPE 3均可降低所有选定细胞趋化因子的表达水平。