ADVANCED MAILLARD REACTION END-PRODUCTS ARE ASSOCIATED WITH ALZHEIMER-DISEASE PATHOLOGY
ADVANCED MAILLARD REACTION END-PRODUCTS ARE ASSOCIATED WITH ALZHEIMER-DISEASE PATHOLOGY
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DOI：
10.1073/pnas.91.12.5710
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发表时间：
1994-06-07
影响因子：
11.1
通讯作者：
PERRY, G
中科院分区：
文献类型：
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作者：
SMITH, MA;TANEDA, S;PERRY, G
在衰老过程中，长寿的蛋白质积累了特定的翻译后修饰。一类修饰，称为美拉德反应产物，是由蛋白质的氨基和还原糖之间的缩合引起的。美拉德反应对蛋白质的修饰与交联的形成、蛋白质溶解度的降低和蛋白酶抗性的增加有关。在这里，我们提出的证据表明，与阿尔茨海默病相关的特征性病理结构包含晚期美拉德反应终产物的典型修饰。具体来说，针对两种美拉德终产物，吡啶和戊苷的抗体，免疫细胞化学标记了阿尔茨海默病患者脑组织中的神经原纤维缠结和老年斑。相比之下，在同一大脑的明显健康的神经元中很少或没有观察到染色。本文描述的美拉德反应相关修饰可以通过形成蛋白质交联来解释阿尔茨海默病病变的生化和不溶性特性。
During aging long-lived proteins accumulate specific post-translational modifications. One family of modifications, termed Maillard reaction products, are initiated by the condensation between amino groups of proteins and reducing sugars. protein modification by the Maillard reaction is associated with crosslink formation, decreased protein solubility, and increased protease resistance. Here, we present evidence that the characteristic pathological structures associated with Alzheimer disease contain modifications typical of advanced Maillard reaction end products. Specifically, antibodies against two Maillard end products, pyrraline and pentosidine, immunocytochemically label neurofibrillary tangles and senile plaques in brain tissue from patients with Alzheimer disease. In contrast, little or no staining is observed in apparently healthy neurons of the same brain. The Maillard-reaction-related modifications described herein could account for the biochemical and insolubility properties of the lesions of Alzheimer disease through the formation of protein crosslinks.