Yu Chun Jiang, Ma Dongying, Song Ling Ling, Zhai Zhen Nan, Tao Ye, Zhang Ying, Cai Ling Yu, Hou Ya Hui, Chen Hong Yuan, Wang Li
Department of Neurology, Second Affiliated Hospital of the Harbin Medical University, China.
Department of Neurosurgery, Second Affiliated Hospital of the Harbin Medical University, China.
Adv Clin Exp Med. 2020 Jun;29(6):661-668. doi: 10.17219/acem/121007.
New glucagon-like peptide-1 (GLP-1) analogues developed in recent years have a long half-life and offer further prospects for clinical application. At present, the neuroprotection of GLP-1 analogues in Alzheimer's disease (AD) has just begun to be explored.
To investigate how glucagon-like peptide-1 (liraglutide) plays a protective role in AD by regulating tau activation and BACE1 expression.
Human neuroblastoma cell line SH-SY5Y cells were cultured in vitro and pretreated with different concentrations of liraglutide, and then treated with different concentrations of okadaic acid (OA) in order to observe the apoptosis of the SH-SY5Y cells. After liraglutide treatment, the apoptosis of neurons in AD rats was detected using flow cytometry, and tau activation and β-site APP cleaving enzyme 1 (BACE1) expression were detected using western blot.
Different concentrations of OA were able to induce apoptosis of SH-SY5Y cells in a dose-dependent manner. Different concentrations of liraglutide were used to pretreat SH-SY5Y cells, which were able to protect the SH-SY5Y cells from apoptosis induced by OA. Okadaic acid significantly increased tau activation and BACE1 expression in the SH-SY5Y cells, which was blocked with liraglutide pretreatment. The results of a water maze experiment showed that liraglutide had significant protective effects on memory and cognitive ability in AD rats induced with OA, inhibited apoptosis of neural cells in AD rats, and inhibited tau activation and BACE1 expression of neural cells in AD rats induced with OA.
Liraglutide has a protective effect on AD in vivo and in vitro, which may be mediated by preventing neuronal apoptosis and inhibiting the activation of tau and the expression of BACE1.
近年来研发的新型胰高血糖素样肽-1（GLP-1）类似物具有较长的半衰期，为临床应用提供了更多前景。目前，GLP-1类似物在阿尔茨海默病（AD）中的神经保护作用刚刚开始被探索。
研究胰高血糖素样肽-1（利拉鲁肽）如何通过调节tau蛋白激活和β-分泌酶1（BACE1）表达在AD中发挥保护作用。
体外培养人神经母细胞瘤细胞系SH-SY5Y细胞，用不同浓度的利拉鲁肽预处理，然后用不同浓度的冈田酸（OA）处理，以观察SH-SY5Y细胞的凋亡情况。利拉鲁肽处理后，采用流式细胞术检测AD大鼠神经元的凋亡情况，采用蛋白质免疫印迹法检测tau蛋白激活和β-位点淀粉样前体蛋白裂解酶1（BACE1）表达。
不同浓度的OA能够以剂量依赖的方式诱导SH-SY5Y细胞凋亡。用不同浓度的利拉鲁肽预处理SH-SY5Y细胞，能够保护SH-SY5Y细胞免受OA诱导的凋亡。冈田酸显著增加SH-SY5Y细胞中tau蛋白的激活和BACE1表达，而利拉鲁肽预处理可阻断这种增加。水迷宫实验结果表明，利拉鲁肽对OA诱导的AD大鼠的记忆和认知能力具有显著的保护作用，抑制AD大鼠神经细胞的凋亡，并抑制OA诱导的AD大鼠神经细胞中tau蛋白的激活和BACE1表达。
利拉鲁肽在体内和体外对AD均有保护作用，其机制可能是通过防止神经元凋亡以及抑制tau蛋白激活和BACE1表达来介导的。
