ROLE OF ABNORMALLY PHOSPHORYLATED TAN IN THE BREAKDOWN OF MICROTUBULES IN ALZHEIMER-DISEASE
ROLE OF ABNORMALLY PHOSPHORYLATED TAN IN THE BREAKDOWN OF MICROTUBULES IN ALZHEIMER-DISEASE
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DOI：
10.1073/pnas.91.12.5562
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发表时间：
1994-06-07
影响因子：
11.1
通讯作者：
IQBAL, K
中科院分区：
文献类型：
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作者：
ALONSO, AD;ZAIDI, T;IQBAL, K
研究了从阿尔茨海默病(AD)和对照组脑中分离的不同tau蛋白的微管组装促进活性以及去磷酸化对这一活性的影响。从2.5%的AD脑高氯酸提取物中分离得到的tau的活性与从对照脑中获得的活性几乎相同，并且这种活性在去磷酸化后没有显著变化。从AD患者脑匀浆中分离出的异常磷酸化tau(ADP-tau)活性很低，经碱性磷酸酶去磷酸化后，其活性增加到与酸溶tau大致相同的水平。在正常tau和微管蛋白混合物中加入AD P-tau可抑制微管组装。AdP-tau与正常的棕褐色结合，但不与微管蛋白结合。这些研究表明，tau的异常磷酸化可能是AD患者受影响神经元中微管破裂的原因，这不仅是因为改变的蛋白几乎没有促进微管的活性，还因为它与正常的tau相互作用，使后者无法促进微管蛋白组装成微管。
The microtubule assembly-promoting activity of different pools of tau protein isolated from Alzheimer disease (AD) and control brains and the effect of dephosphorylation on this activity were studied. Tau isolated from a 2.5% perchloric extract of AD brain had almost the same activity as that obtained from control brain, and this activity did not change significantly on dephosphorylation. Abnormally phosphorylated tau (AD P-tau) isolated from brain homogenate of AD patients had little activity, and upon dephosphorylation with alkaline phosphatase, its activity increased to approximately the same level as the acid-soluble tau. Addition of AD P-tau to a mixture of normal tau and tubulin inhibited microtubule assembly. AD P-tau bound to normal tan but not to tubulin. These studies suggest that the abnormal phosphorylation of tau might be responsible for the breakdown of microtubules in affected neurons in AD not only because the altered protein has little microtubule-promoting activity but also because it interacts with normal tau, making the latter unavailable for promoting the assembly of tubulin into microtubules.