DEFECTIVE BRAIN MICROTUBULE ASSEMBLY IN ALZHEIMER'S DISEASE
DEFECTIVE BRAIN MICROTUBULE ASSEMBLY IN ALZHEIMER'S DISEASE
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DOI：
10.1016/s0140-6736(86)92134-3
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发表时间：
1986-08
期刊：
影响因子：
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通讯作者：
K. Iqbal;T. Zaidi;GuangY. Wen;I. Grundke‐Iqbal;P. Merz;Sadia Shaikh;H. Wisniewski;I. Alafuzoff-I.-Alafu
中科院分区：
文献类型：
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作者：
K. Iqbal;T. Zaidi;GuangY. Wen;I. Grundke‐Iqbal;P. Merz;Sadia Shaikh;H. Wisniewski;I. Alafuzoff-I.-Alafu
对死后2-4小时内获得的经组织病理学证实为阿尔茨海默病的脑和来自匹配年龄的对照组的非阿尔茨海默病的脑进行了微管和神经丝的体外组装。微管组装只在对照组观察到，但在阿尔茨海默病脑中没有观察到，神经丝从两种类型的脑中获得。微管相关蛋白tau刺激微管从微管蛋白组装，在阿尔茨海默病患者中被异常磷酸化，但在对照脑微管制备中没有。阿尔茨海默病患者的大脑没有显示出任何微管组装抑制物的存在或微管蛋白的任何异常。DEAE-葡聚糖是一种模拟tau刺激微管组装的聚阳离子，它诱导了阿尔茨海默病大脑中微管的组装。用抗α微管蛋白酪氨酸化羧基末端表位的单抗将正常和阿尔茨海默病患者脑中的微管蛋白标记在蛋白质印迹上。这些研究表明，在阿尔茨海默病中，微管蛋白可以组装成大脑微管，但这个过程是有缺陷的，可能是因为tau的异常磷酸化。Tau的这种翻译后改变可能是阿尔茨海默病神经原纤维异常的原因。
Brains obtained within 2-4 hours post mortem and histopathologically confirmed for Alzheimer's disease and non-Alzheimer brains from agematched controls were examined for in-vitro assembly of microtubules and neurofilaments. Microtubule assembly was observed only in control but not in Alzheimer brains, and neurofilaments were obtained from both types of brain. The microtubule-associated protein tau, which stimulates assembly of microtubules from tubulin, was abnormally phosphorylated in Alzheimer but not in control brain microtubule preparations. Alzheimer brains did not show the presence of any inhibitor of microtubule assembly or any abnormality of tubulin. DEAE-dextran, a polycation which mimics tau in stimulating microtubule assembly, induced the assembly of microtubules in Alzheimer brain. Tubulin from both normal and Alzheimer brains was labelled on western blots by a monoclonal antibody to the tyrosinylated carboxy-terminal epitope of α tubulin. These studies suggest that in Alzheimer's disease tubulin can be assembled into brain microtubules, but the process is defective, probably because of abnormal phosphorylation of tau. This post-translational alteration of tau might be the cause of the neurofibrillary abnormality in Alzheimer's disease.