Alonso A C, Zaidi T, Grundke-Iqbal I, Iqbal K
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5562-6. doi: 10.1073/pnas.91.12.5562.
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 tau 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.
研究了从阿尔茨海默病（AD）患者大脑和对照大脑中分离出的不同tau蛋白组分的微管组装促进活性，以及去磷酸化对该活性的影响。从AD脑的2.5%高氯酸提取物中分离出的tau与从对照脑中获得的tau具有几乎相同的活性，并且该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（AD P-tau）活性很低，在用碱性磷酸酶去磷酸化后，其活性增加到与酸溶性tau大致相同的水平。将AD P-tau添加到正常tau和微管蛋白的混合物中会抑制微管组装。AD P-tau与正常tau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中受影响神经元微管破坏的原因，这不仅是因为改变后的蛋白几乎没有微管促进活性，还因为它与正常tau相互作用，使后者无法促进微管蛋白组装成微管。
