Qi Liqin, Chen Zhou, Wang Yanping, Liu Xiaoying, Liu Xiaohong, Ke Linfang, Zheng Zhongjie, Lin Xiaowei, Zhou Yu, Wu Lijuan, Liu Libin
Department of Endocrinology, Fujian Institute of Endocrinology, Fujian Medical University Union Hospital Fuzhou, Fujian, People's Republic of China.
Department of Pharmacology, College of Pharmacy, Fujian Medical University Fuzhou, Fujian, People's Republic of China.
Am J Transl Res. 2017 Feb 15;9(2):247-260. eCollection 2017.
Memory deterioration and synapse damage with accumulation of β-amyloid and hyperphosphorylated tau are hallmark lesions of Alzheimer's disease (AD). Methylglyoxal (MG), a key intermediate of glucose metabolism, is elevated in AD brains and modifies Aβ, increasing misfolding and leading to the accumulation of senile plaques. Liraglutide, an analog of glucagon-like peptide-1 (GLP-1), is neurotrophic and neuroprotective. However, whether liraglutide can protect against AD-like memory-related deficits and tau hyperphosphorylation caused by MG in vivo is not known. Here, we report that MG induces tau hyperphosphorylation and causes ultrastructural hippocampal damage and cognitive impairment in C57BL/6J mice. Liraglutide reduced these effects via activation of the protein kinase B and glycogen synthase kinase-3β pathways. Our data reveal that liraglutide may alleviate AD-like cognitive impairment by decreasing the phosphorylation of tau.
β-淀粉样蛋白的积累以及tau蛋白的过度磷酸化所导致的记忆衰退和突触损伤是阿尔茨海默病（AD）的标志性病变。甲基乙二醛（MG）是葡萄糖代谢的关键中间体，在AD患者大脑中含量升高，并修饰β-淀粉样蛋白（Aβ），增加其错误折叠，导致老年斑的积累。利拉鲁肽是胰高血糖素样肽-1（GLP-1）的类似物，具有神经营养和神经保护作用。然而，利拉鲁肽在体内是否能够预防由MG引起的类似AD的记忆相关缺陷和tau蛋白过度磷酸化尚不清楚。在此，我们报告MG诱导C57BL/6J小鼠tau蛋白过度磷酸化，导致海马超微结构损伤和认知障碍。利拉鲁肽通过激活蛋白激酶B和糖原合酶激酶-3β途径减轻了这些影响。我们的数据表明，利拉鲁肽可能通过减少tau蛋白的磷酸化来缓解类似AD的认知障碍。
