School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
Life Sci. 2019 Mar 15;221:35-46. doi: 10.1016/j.lfs.2019.02.012. Epub 2019 Feb 5.
Alzheimer's disease (AD), a neurodegenerative disease, is characterized by memory loss and synaptic damage. Up to now, there are limited drugs to cure or delay the state of this illness. Recently, the Fyn tyrosine kinase is implicated in AD pathology triggered by synaptic damage. Thus, Fyn inhibition may prevent or delay the AD progression. Therefore, in this paper, we investigated whether Panaxadiol could decrease synaptic damage in AD and the underlying mechanism.
The ability of learning and memory of mice has detected by Morris Water Maze. The pathological changes detected by H&E staining and Nissl staining. The percentage of cell apoptosis and the calcium concentration were detected by Flow Cytometry in vitro. The amount of synaptic protein and related proteins in the Fyn/GluN2B/CaMKIIα signaling pathway were detected by Western Blot.
In the present article, Panaxadiol could significantly improve the ability of learning and memory of mice and reduce its synaptic dysfunction. Panaxadiol could down-regulate GluN2B's phosphorylation level by inhibition Fyn kinase activity, Subsequently, decrease Ca-mediated synaptic damage, reducing LDH leakage, inhibiting apoptosis in AD, resulting in facilitating the cells survival. For the underlying molecular mechanism, we used PP2 to block the Fyn/GluN2B/CaMKIIα signaling pathway. The results from WB showed that the expression of related proteins in the Fyn signaling pathway decreased with PP2 treated.
Our results indicate that Panaxadiol could decrease synaptic damage, which will cause AD via inhibition of the Fyn/GluN2B/CaMKIIα signaling pathway. Thus, the Panaxadiol is a best promising candidate to test as a potential therapy for AD.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是记忆丧失和突触损伤。到目前为止，治疗或延缓这种疾病的药物有限。最近，Fyn 酪氨酸激酶在突触损伤引发的 AD 病理学中被牵连。因此，抑制 Fyn 可能会阻止或延缓 AD 的进展。因此，在本文中，我们研究了人参二醇是否可以减少 AD 中的突触损伤及其潜在机制。
通过 Morris 水迷宫检测小鼠的学习和记忆能力。通过 H&E 染色和尼氏染色检测病理变化。通过流式细胞术体外检测细胞凋亡百分比和钙浓度。通过 Western Blot 检测 Fyn/GluN2B/CaMKIIα 信号通路中的突触蛋白和相关蛋白的含量。
在本文中，人参二醇可以显著改善小鼠的学习和记忆能力，减少其突触功能障碍。人参二醇通过抑制 Fyn 激酶活性，下调 GluN2B 的磷酸化水平，从而减少 Ca 介导的突触损伤，减少 LDH 渗漏，抑制 AD 中的细胞凋亡，促进细胞存活。对于潜在的分子机制，我们使用 PP2 阻断 Fyn/GluN2B/CaMKIIα 信号通路。WB 的结果表明，用 PP2 处理后，Fyn 信号通路中相关蛋白的表达减少。
我们的结果表明，人参二醇可以通过抑制 Fyn/GluN2B/CaMKIIα 信号通路减少突触损伤，从而导致 AD。因此，人参二醇是作为 AD 潜在治疗方法的最佳候选药物。
