Neuroprotective potency of anti-hyperglycemic agent 1-deoxynojirimycin

脑胰岛素抵抗往往早在阿尔茨海默病（AD）发病前就出现了。因此，我们评估了1-脱氧诺吉霉素（DNJ），一种糖糖和胰岛素增敏剂，在神经元胰岛素抵抗的细胞培养模型中缓解AD症状的效果。通过评估胰岛素信号成分和AD标志物的变化，我们发现DNJ: 1)通过促进AKT/GSK3B级联逆转神经元胰岛素抵抗；2)通过Ser9磷酸化抑制GSK3B活性（一种主要的tau激酶）减轻tau过度磷酸化；3)增加胰岛素降解酶（Ide）的表达，这可能有助于清除淀粉样蛋白-β并降低其积累。总的来说，这些数据为DNJ的神经保护机制提供了新的见解，即通过保持神经元胰岛素敏感性。

Brain insulin resistance often precedes Alzheimer’s disease (AD) long before its onset. We thereby assessed the use of 1-deoxynojirimycin (DNJ), an aza-sugar and insulin sensitizer, to relieve AD symptoms in cell culture model of neuronal insulin resistance. By assessing the changes in insulin signaling components and AD markers, we found that DNJ: 1) reverses neuronal insulin resistance by promoting AKT/GSK3B cascade: 2) attenuates tau hyperphosphorylation by inhibiting GSK3B activity (a major tau kinase) via Ser9 phosphorylation; 3) increases the expression of insulin-degrading enzyme (Ide), which may help to clear amyloid-β and lower its accumulation. Overall, this data provides novel insight into the neuroprotective mechanism of DNJ, that is, by preserving neuronal insulin sensitivity.