当前位置:
X-MOL 学术
›
J. Neurochem.
›
论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Increased glutaminyl cyclase activity in brains of Alzheimer’s disease individuals
Journal of Neurochemistry ( IF 4.7 ) Pub Date : 2020-07-02 , DOI: 10.1111/jnc.15114 Adam P Gunn 1, 2 , Bruce X Wong 3 , Catriona McLean 4 , Chris Fowler 1 , Peter J Barnard 5 , James A Duce 1, 3 , Blaine R Roberts 1, 6, 7 ,
Journal of Neurochemistry ( IF 4.7 ) Pub Date : 2020-07-02 , DOI: 10.1111/jnc.15114 Adam P Gunn 1, 2 , Bruce X Wong 3 , Catriona McLean 4 , Chris Fowler 1 , Peter J Barnard 5 , James A Duce 1, 3 , Blaine R Roberts 1, 6, 7 ,
Affiliation
Glutaminyl cyclases (QC) catalyze the formation of neurotoxic pGlu‐modified amyloid‐β peptides found in the brains of people with Alzheimer's disease (AD). Reports of several‐fold increases in soluble QC (sQC) expression in the brain and peripheral circulation of AD individuals has prompted the development of QC inhibitors as potential AD therapeutics. There is, however, a lack of standardized quantitative data on QC expression in human tissues, precluding inter‐laboratory comparison and validation. We tested the hypothesis that QC is elevated in AD tissues by quantifying levels of sQC protein and activity in post‐mortem brain tissues from AD and age‐matched control individuals. We found a modest but statistically significant increase in sQC protein, which paralleled a similar increase in enzyme activity. In plasma samples sourced from the Australian Imaging, Biomarker and Lifestyle study we determined that QC activity was not different between the AD and control group, though a modest increase was observed in female AD individuals compared to controls. Plasma QC activity was further correlated with levels of circulating monocytes in AD individuals. These data provide quantitative evidence that alterations in QC expression are associated with AD pathology.
中文翻译:
阿尔茨海默氏病个体大脑中的谷氨酰胺酰环化酶活性增加
谷氨酰胺基环化酶(QC)催化在阿尔茨海默氏病(AD)的人脑中发现的神经毒性pGlu修饰的淀粉样β肽的形成。关于AD个体的大脑和外周循环中可溶性QC(sQC)表达增加数倍的报道促使了QC抑制剂作为潜在的AD治疗药物的发展。但是,缺乏关于人体组织中QC表达的标准化定量数据,无法进行实验室间的比较和验证。我们通过量化AD和年龄匹配的对照个体的死后脑组织中sQC蛋白的水平和活性,检验了AD组织中QC升高的假说。我们发现sQC蛋白有适度但有统计学意义的增加,与酶活性的类似增加平行。在来自澳大利亚影像,生物标志物和生活方式研究的血浆样本中,我们确定了AD和对照组之间的QC活性没有差异,尽管与对照相比女性AD个体的QC活性有所增加。血浆QC活性与AD个体中循环单核细胞水平进一步相关。这些数据提供了定量证据,证明QC表达的改变与AD病理相关。
更新日期:2020-07-02
中文翻译:
阿尔茨海默氏病个体大脑中的谷氨酰胺酰环化酶活性增加
谷氨酰胺基环化酶(QC)催化在阿尔茨海默氏病(AD)的人脑中发现的神经毒性pGlu修饰的淀粉样β肽的形成。关于AD个体的大脑和外周循环中可溶性QC(sQC)表达增加数倍的报道促使了QC抑制剂作为潜在的AD治疗药物的发展。但是,缺乏关于人体组织中QC表达的标准化定量数据,无法进行实验室间的比较和验证。我们通过量化AD和年龄匹配的对照个体的死后脑组织中sQC蛋白的水平和活性,检验了AD组织中QC升高的假说。我们发现sQC蛋白有适度但有统计学意义的增加,与酶活性的类似增加平行。在来自澳大利亚影像,生物标志物和生活方式研究的血浆样本中,我们确定了AD和对照组之间的QC活性没有差异,尽管与对照相比女性AD个体的QC活性有所增加。血浆QC活性与AD个体中循环单核细胞水平进一步相关。这些数据提供了定量证据,证明QC表达的改变与AD病理相关。