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首页> 外文期刊>Neuropharmacology >Methylene blue activates the PMCA activity and cross-interacts with amyloid beta-peptide, blocking A beta-mediated PMCA inhibition
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Methylene blue activates the PMCA activity and cross-interacts with amyloid beta-peptide, blocking A beta-mediated PMCA inhibition

机译：亚甲蓝激活PMCA活性并用淀粉样蛋白β-肽交互，阻断β介导的PMCA抑制作用

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摘要

The phenothiazine methylene blue (MB) is attracting increasing attention because it seems to have beneficial effects in the pathogenesis of Alzheimer's disease (AD). Among other factors, the presence of neuritic plaques of amyloid-beta peptide (A(3) aggregates, neurofibrilar tangles of tau and perturbation of cytosolic Ca2+ are important players of the disease. It has been proposed that MB decreases the formation of neuritic plaques due to A beta aggregation. However, the molecular mechanism underlying this effect is far from clear. In this work, we show that MB stimulates the Ca2+-ATPase activity of the plasma membrane Ca2+-ATPase (PMCA) in human tissues from AD-affected brain and age-matched controls and also from pig brain and cell cultures. In addition, MB prevents and even blocks the inhibitory effect of A beta on PMCA activity. Functional analysis with mutants and fluorescence experiments strongly suggest that MB binds to PMCA, at the C-terminal tail, in a site located close to the last transmembrane helix and also that MB binds to the peptide. Besides, A beta. increases PMCA affinity for MB. These results point out a novel molecular basis of MB action on A beta and PMCA as mediator of its beneficial effect on AD. (C) 2018 Elsevier Ltd. All rights reserved.
机译：吩噻嗪亚甲基蓝（MB）吸引了越来越多的关注，因为它似乎对阿尔茨海默病的发病机制（AD）具有有益的影响。在其他因素中，淀粉样蛋白 - β肽（A（3）聚集体，Tau的神经纤维缠结的神经斑块和细胞源CA2 +的扰动是所述疾病的重要参与者。已经提出MB降低了神经能量斑块的形成对于β聚集。然而，这种效果的分子机制远非清晰。在这项工作中，我们表明MB刺激来自AD受影响的大脑的人组织中血浆膜Ca2 + -ATP酶（PMCA）的Ca2 + -AtPase活性和年龄匹配的对照和猪脑和细胞培养物。此外，MB可防止甚至阻断β对PMCA活性的抑制作用。具有突变体和荧光实验的功能分析强烈表明MB与PMCA结合，在C处结合PMCA - 尾巴，在靠近最后一个跨膜螺旋的部位，也是Mb与肽结合的。此外，β。对MB的PMCA亲和力增加。这些结果指出了一种新的分子基础在Beta和PMCA上的MB行动作为其对广告有益效果的调解员。 （c）2018年elestvier有限公司保留所有权利。

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