GLUCAGON-LIKE PEPTIDE-1 PROTECTS HIPPOCAMPAL NEURONS AGAINST ADVANCED GLYCATION END PRODUCT-INDUCED TAU HYPERPHOSPHORYLATION
GLUCAGON-LIKE PEPTIDE-1 PROTECTS HIPPOCAMPAL NEURONS AGAINST ADVANCED GLYCATION END PRODUCT-INDUCED TAU HYPERPHOSPHORYLATION
复制标题
胰高血糖素样肽-1 保护海马神经元免受晚期糖基化终产物诱导的 tau 蛋白过度磷酸化
DOI：
10.1016/j.neuroscience.2013.10.038
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发表时间：
2014-01-03
期刊：
影响因子：
3.3
通讯作者：
Gao, X. -D.
中科院分区：
文献类型：
--
作者：
Chen, S.;An, F. -M.;Gao, X. -D.
我们先前已经证明，胰高血糖素样肽-1（GLP-1）受体激动剂改善糖尿病相关阿尔茨海默病（AD）大鼠模型的神经退行性变化，并保护神经元免受体外葡萄糖毒性。本研究以PC 12细胞和原代海马神经元为研究对象，探讨GLP-1受体介导物对糖基化终产物（AGEs）诱导的细胞毒性和tau蛋白过度磷酸化的影响及其分子机制。我们的研究表明，GLP-1在高血糖条件下与葡萄糖-牛血清白蛋白（BSA）处理的PC 12细胞中存在类似的保护作用，或单独与glycoprotein-BSA。此外，单独的葡萄糖-BSA在PC 12细胞中没有诱导显著的细胞毒性，但在24 h内导致原代海马神经元中tau蛋白过度磷酸化。我们发现GLP-1可以降低高糖或葡萄糖-BSA诱导的细胞tau蛋白磷酸化。此外，我们在本研究中的数据表明，GLP-1通过涉及糖原合成酶激酶3 β（GSK-3 β）的信号通路调节AGEs诱导的tau磷酸化，与GSK-3 β抑制剂氯化锂相似。我们的研究结果表明，GLP-1可以保护神经元免受糖尿病相关的AGE损伤，并提供了新的证据，GLP-1受体激动剂在治疗AD，特别是糖尿病相关的AD的潜在治疗价值。(C)2013年IBRO。由爱思唯尔有限公司出版。保留所有权利。
We have previously demonstrated that glucagon-like peptide-1 (GLP-1) receptor agonist ameliorated neurodegenerative changes in rat models of diabetes-related Alzheimer's disease (AD), and protected neurons from glucose toxicity in vitro. Herein, we investigated the effects of GLP-1 receptor mediates on cell toxicity and tau hyperphosphorylation induced by advanced glycation end products (AGEs), which are associated with glucose toxicity, and the molecular mechanism in PC12 cells and the primary hippocampal neurons. Our study demonstrated that the similar protection effects of GLP-1 existed in PC12 cells treated with glucose-bovine serum albumin (BSA) in hyperglycemic conditions or with glycoaldehyde-BSA alone. Additionally, glucose-BSA alone did not induce significant cytotoxicity in PC12 cells, but resulted in tau hyperphosphorylation in primary hippocampal neurons in 24 h. And we found that GLP-1 could reduce cell tau phosphorylation induced by high glucose or glucose-BSA. Furthermore, our data in the present study suggested that GLP-1 regulated tau phosphorylation induced by AGEs through a signaling pathway involving glycogen synthase kinase 3 beta (GSK-3 beta), similarly to the GSK-3 beta inhibitor, lithium chloride. Our findings suggest that GLP-1 can protect neurons from diabetes-associated AGE insults in vitro, and provide new evidence for a potential therapeutic value of GLP-1 receptor agonist in the treatment of AD especially diabetes-related AD. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.