利西拉肽对阿尔茨海默病保护作用机制的研究进展

Lixisenatide Research Progress of Protection Mechanism of Alzheimer's Disease

近年来,越来越多的临床和实验数据表明2型糖尿病与阿尔茨海默病之间关系密切。2型糖尿病和阿尔茨海默病具有共同的病理生理特征:β淀粉样蛋白沉积、tau蛋白过磷酸化和葡萄糖合成酶3活性增加。研究发现2型糖尿病患者患阿尔茨海默病的风险与正常人比较有增加的趋势。对阿尔茨海默病动物模型脑组织进行研究,结果表明应用胰高血糖素样肽1类似物治疗后,脑内胰岛素抵抗得到改善,四羟壬烯酸、丙二醛等氧化应激指标显著减少,而其他病理特征有逆转的趋势,特别是新型的胰高血糖素样肽1受体激动剂利西拉肽作用更显著,且不良反应事件更少。最新文献证实利西拉肽具有神经保护作用,可用于阿尔茨海默病的治疗。文中就利西拉肽在阿尔茨海默病中的作用做一综述。

In recent years, more and more clinical and experimental evidence showed that type 2 diabetes mellitus（T2DM） is closely related to Alzheimer＇s disease（AD）. T2 DM and AD have the common pathophysiological characteristics in the aspects of amyloid beta deposition, Tau protein phosphorylation and glucose synthase 3 activity increased. It was found that the risk of developing AD in patients with T2 DM was more likely to be increased compared with normal subjects. After animal model of AD brain tissue were studied, the results showed that the brain insulin resistance improved, MDA and 4-hydroxynonenal（4-HNE） indicators of oxidative stress significantly reduced and other pathological characteristics were reversed after the application of glucagon like peptide 1 analogues, especially the effect of lixisenatide more significantly. The results provide a theoretical basis for the GLP-1 analogues of AD potential therapeutic. The neuroprotective effect of lixisenatide in AD were reviewed.