Alzheimer-specific epitopes of tau represent lipid peroxidation-induced conformations
Alzheimer-specific epitopes of tau represent lipid peroxidation-induced conformations
复制标题
DOI：
10.1016/j.freeradbiomed.2004.11.005
复制
发表时间：
2005-03-15
影响因子：
7.4
通讯作者：
Perry, G
中科院分区：
文献类型：
--
作者：
Liu, Q;Smith, MA;Perry, G
最近的几项研究支持tau蛋白磷酸化和tau通过活性羰基的加合之间的联系。事实上，由脂质过氧化产生的羰基产物对tau蛋白的磷酸化依赖性加合产生了神经元缠结相关抗原Alz 50。为了确定羰基修饰的tau蛋白的表位是否是与神经元缠结形成相关的主要构象变化，我们检查了针对神经元缠结产生的七种不同抗体，这些抗体识别阿尔茨海默病中tau蛋白的独特表位。一致地，所有七种抗体在用反应性羰基4-羟基-2-壬烯醛（HNE）处理正常tau后更强烈地识别tau（4至34倍），但仅当tau处于磷酸化状态时。这些发现不仅支持氧化应激参与阿尔茨海默病患者大脑中发生的神经元缠结形成的观点，而且还首次表明，tau蛋白的HNE修饰促进并有助于产生定义神经元缠结的主要构象特性。(C)2004年爱思唯尔公司All rights reserved.
Several recent studies support a link between tau protein phosphorylation and adduction of tau by reactive carbonyls. Indeed, the phosphorylation-dependent adduction of tau by carbonyl products resulting from lipid peroxidation creates the neurofibrillary tangle-related antigen, Alz50. To determine whether epitopes of carbonyl-modified tau are major conformational changes associated with neurofibrillary tangle formation, we examined seven distinct antibodies raised against neurofibrillary tangles that recognize unique epitopes of tau in Alzheimer disease. Consistently, all seven antibodies recognize tau more strongly (4- to 34-fold) after treatment of normal tau with the reactive carbonyl, 4-hydroxy-2-nonenal (HNE), but only when tau is in the phosphorylated state. These findings not only support the idea that oxidative stress is involved in neurofibrillary tangle formation occurring in brains of Alzheimer disease patients, but also show, for the first time, that HNE modifications of tau promote and contribute to the generation of the major conformational properties defining neurofibrillary tangles. (C) 2004 Elsevier Inc. All rights reserved.