What is the new target inhibiting the progression of Alzheimer's disease?  

作　　者：Lin Zhang Jing Yang Yunpeng Cao 

机构地区：[1]Department of Neurology, First Affiliated Hospital of China Medical University [2]Provincial Key Laboratory of Cardiovascular and Cerebrovascular Drug Basic Research, Liaoning Medical University

出　　处：《Neural Regeneration Research》2013年第21期1938-1947,共10页中国神经再生研究（英文版）

摘　　要：To stop the progression of Alzheimer＇s disease in the early stage, it is necessary to identify new therapeutic targets. We examined striatal-enriched phosphatase 61 expression in the brain tissues of 12-month-old APPswe/PSEN1dE9 transgenic mice. Immunohistochemistry showed that striatal-enriched phosphatase 61 protein expression was significantly increased but phosphorylated N-methyl-D-aspartate receptor 2B levels were significantly decreased in the cortex and hippocampus of APPswe/PSEN1dE9 transgenic mice. Western blotting of a cell model of Alzheimer＇s disease consisting of amyloid-beta peptide （1-42）-treated C57BL/6 mouse cortical neurons in vitro showed that valeric acid （AP5）, an N-methyl-D-aspartate receptor antagonist, significantly inhibited amyloidbeta 1-42-induced increased activity of striatal-enriched phosphatase 61. In addition, the phosphorylation of N-methyl-D-aspartate receptor 2B at Tyr1472 was impaired in amyloid-beta 1-42-treated cortical neurons, but knockdown of striatal-enriched phosphatase 61 enhanced the phosphorylation of N-methyl-D-aspartate receptor 2B. Collectively, these findings indicate that striatal-enriched phosphatase 61 can disturb N-methyl-D-aspartate receptor transport and inhibit the progression of learning and study disturbances induced by Alzheimer＇s disease. Thus, striatal-enriched phosphatase 61 may represent a new target for inhibiting the progression of Alzheimer＇s disease.To stop the progression of Alzheimer＇s disease in the early stage, it is necessary to identify new therapeutic targets. We examined striatal-enriched phosphatase 61 expression in the brain tissues of 12-month-old APPswe/PSEN1dE9 transgenic mice. Immunohistochemistry showed that striatal-enriched phosphatase 61 protein expression was significantly increased but phosphorylated N-methyl-D-aspartate receptor 2B levels were significantly decreased in the cortex and hippocampus of APPswe/PSEN1dE9 transgenic mice. Western blotting of a cell model of Alzheimer＇s disease consisting of amyloid-beta peptide （1-42）-treated C57BL/6 mouse cortical neurons in vitro showed that valeric acid （AP5）, an N-methyl-D-aspartate receptor antagonist, significantly inhibited amyloidbeta 1-42-induced increased activity of striatal-enriched phosphatase 61. In addition, the phosphorylation of N-methyl-D-aspartate receptor 2B at Tyr1472 was impaired in amyloid-beta 1-42-treated cortical neurons, but knockdown of striatal-enriched phosphatase 61 enhanced the phosphorylation of N-methyl-D-aspartate receptor 2B. Collectively, these findings indicate that striatal-enriched phosphatase 61 can disturb N-methyl-D-aspartate receptor transport and inhibit the progression of learning and study disturbances induced by Alzheimer＇s disease. Thus, striatal-enriched phosphatase 61 may represent a new target for inhibiting the progression of Alzheimer＇s disease.

关 键 词：neural regeneration brain injury NEURODEGENERATION Alzheimer’s disease striatal-enriched phosphatase 61 amyloid-beta peptide N-methyl-D-aspartate receptor GluN2B RNA interference immunohistochemistry western blot NEUROREGENERATION 

分 类 号：R749.16[医药卫生—神经病学与精神病学]