Yoshino Yuta, Ishisaka Mitsue, Tsujii Saori, Shimazawa Masamitsu, Hara Hideaki
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
Biochem Biophys Res Commun. 2015 Mar 6;458(2):274-9. doi: 10.1016/j.bbrc.2015.01.098. Epub 2015 Feb 7.
Alzheimer's disease (AD) is a common neurodegenerative disease characterized by cognitive dysfunction and neuronal cell death in the hippocampus and cerebral cortex. Glucagon-like peptide-1 (GLP-1) is an insulinotropic peptides. GLP-1-associated medicines are widely used as treatments for type 2 diabetes. In addition, they have been shown to ameliorate pathology in AD mouse models. Here, we investigated the effects of GLP-1 on different stressors in murine hippocampal HT22 cells. GLP-1 (7-36) prevented H2O2-, l-glutamate-, tunicamycin-, thapsigargin-, and amyloid β1-42-induced neuronal cell death in a concentration-dependent manner. GLP-1 (7-36) treatment for 1 h significantly increased phosphorylated Akt and extracellular signal-regulated kinase 1 and 2 (ERK1/2) when compared with vehicle-treatment. These results suggest that GLP-1 (7-36) is protective against these stressors via activation of survival signaling molecules, such as Akt and ERK1/2 in HT22 cells. In conclusion, GLP-1 and activators of the GLP-1 receptor might be useful targets for the treatment of AD.
阿尔茨海默病（AD）是一种常见的神经退行性疾病，其特征为认知功能障碍以及海马体和大脑皮层中的神经元细胞死亡。胰高血糖素样肽-1（GLP-1）是一种促胰岛素肽。与GLP-1相关的药物被广泛用作2型糖尿病的治疗药物。此外，它们已被证明可改善AD小鼠模型中的病理状况。在此，我们研究了GLP-1对小鼠海马HT22细胞中不同应激源的影响。GLP-1（7-36）以浓度依赖性方式预防了过氧化氢、L-谷氨酸、衣霉素、毒胡萝卜素和淀粉样β1-42诱导的神经元细胞死亡。与溶剂处理相比，GLP-1（7-36）处理1小时显著增加了磷酸化的Akt以及细胞外信号调节激酶1和2（ERK1/2）。这些结果表明，GLP-1（7-36）通过激活HT22细胞中的存活信号分子（如Akt和ERK1/2）来抵御这些应激源。总之，GLP-1和GLP-1受体激动剂可能是治疗AD的有用靶点。
