Carbonyl-related posttranslational modification of neurofilament protein in the neurofibrillary pathology of Alzheimer's disease.
Carbonyl-related posttranslational modification of neurofilament protein in the neurofibrillary pathology of Alzheimer's disease.
复制标题
阿尔茨海默病神经原纤维病理学中神经丝蛋白的羰基相关翻译后修饰。
DOI：
10.1046/j.1471-4159.1995.64062660.x
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发表时间：
1995
影响因子：
4.7
通讯作者：
Perry,G
中科院分区：
文献类型：
--
作者：
Smith,MA;Rudnicka-Nawrot,M;Richey,PL;Praprotnik,D;Mulvihill,P;Miller,CA;Sayre,LM;Perry,G
我们提出了阿尔茨海默病（AD）神经病理学中神经丝羰基相关翻译后修饰的第一个证据。两种不同的单克隆抗体，一贯标记的神经纤维缠结（NFT），神经纤维线程，颗粒空泡变性的部分AD组织也标记的轴突内的神经丝的白色物质后，通过还原糖，戊二醛，甲醛，或丙二醛的修改。由这两种抗体识别的表位显示出对神经丝重亚基的羰基修饰的严格依赖性。在AD的神经病理学中，这种神经丝修饰在体内的发生表明羰基修饰与可能在神经病理学的发病机制中至关重要的全身性细胞骨架异常相关。此外，本文提供的数据支持广泛的翻译后修饰，包括氧化应激型机制，通过形成交联，可能是NFT的生化特性及其体内降解抗性的原因。
We present the first evidence for carbonyl‐related posttranslational modifications of neurofilaments in the neurofibrillary pathology of Alzheimer's disease (AD). Two distinct monoclonal antibodies that consistently labeled neurofibrillary tangles (NFTs), neuropil threads, and granulovacuolar degeneration in sections of AD tissue also labeled the neurofilaments within axons of the white matter following modification by reducing sugars, glutaraldehyde, formaldehyde, or malondialdehyde. The epitope recognized by these two antibodies shows a strict dependency for carbonyl modification of the neurofilament heavy subunit. The in vivo occurrence of this neurofilament modification in the neurofibrillary pathology of AD suggests that carbonyl modification is associated with a generalized cytoskeletal abnormality that may be critical in the pathogenesis of neurofibrillary pathology. Furthermore, the data presented here support the idea that extensive posttranslational modifications, including oxidative stress‐type mechanisms, through the formation of cross‐links, might account for the biochemical properties of NFTs and their resistance to degradation in vivo.