蛋白磷酸酯酶在Alzheimer氏病tau蛋白异常磷酸化中的作用

Effect of Protein Phosphatases on Abnormal Phosphorylationoftau Protein in Alzheimer Disease

用蛋白磷酸酯酸PP-2A、-2B和-1型分别处理的Alzheimer病（AD）异常磷酸化tau蛋白可不同程度恢复其促微管聚集和组装功能。PP－2A的恢复作用比PP－2B和PP－1更强．PP－2A，PP－2B和PP－1使异常tau蛋白水解释放磷酸的量分别为其总量的57％，36％和30％。tau蛋白Ser－235位的磷酸化不是决定其功能的关键位点，而Thr－231的磷酸化可能与微管组装早期的成核聚集作用有关。该研究证明：体内蛋白磷酸酯酶PP－2A，PP－2B和PP－1可能参与tau蛋白异常磷酸化过程，保持这些磷酸酯酶的活性有可能抑制AD神经原纤维退化．

Dephosphorylation of abnormally phosphorylated tau by protein Phosphatase, PP-2A,PP-2B or PP-1 restored its biological activity both in the nucleation and in the assembly of microtobules.Both the amount of phosphate released and the rate of restoration of microtobule-assembly promotingactivity of the abnormal tau were greater on dephosphorylation by PP-2A than PP-2B or PP-1. During90 min incubation at 37℃, PP-2A, PP-2B and PP-1 released respectively -57%, -36% and30% of tau phosphate. Association of the restoration of biological edivity of the abnormal tau dephosphorylated by different phosphatases and the immunological identification of the dephosphorylated sites revealed that ser-235 is not critical in tau function, and the thr-231 is probably involved inthe regulation of the nucleation and not the assembly of microtubules. These studies indicated thatthe phosphorylation of tau in situ might be regUlated by PP-2A, PP-2B and PP-1 and the activation ofthese enzyme activities might arrest the Alzheimer neurofibrillny degeneration.