TAU-PROTEINS OF ALZHEIMER PAIRED HELICAL FILAMENTS - ABNORMAL PHOSPHORYLATION OF ALL 6 BRAIN ISOFORMS
TAU-PROTEINS OF ALZHEIMER PAIRED HELICAL FILAMENTS - ABNORMAL PHOSPHORYLATION OF ALL 6 BRAIN ISOFORMS
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DOI：
10.1016/0896-6273(92)90117-v
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发表时间：
1992-01-01
期刊：
影响因子：
16.2
通讯作者：
CROWTHER, RA
中科院分区：
文献类型：
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作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
阿尔茨海默病和唐氏综合征患者脑中分散的成对螺旋丝（PHF）的制备物在凝胶上显示了三条主要条带，对应于微管相关蛋白tau的异常修饰形式。这种模式的解释是困难的，因为在正常大脑中有六种tau亚型，磷酸化改变了它们的流动性。通过高温下的酶促去磷酸化，我们已经转移了从分散的PHF中获得的三条异常条带，以与六种非磷酸化的tau亚型对齐。通过使用特异性抗体的一些插入，区分各种亚型和标记PHF，我们已经建立了PHF，异常带，和亚型之间的对应关系。这种异构体的鉴定是揭示PHFs分子发病机制的必要步骤。
Preparations of dispersed paired helical filaments(PHFs) from the brains of Alzheimer's disease and Down's syndrome patients display on gels three principal bands corresponding to abnormally modified forms of the microtubule-associated protein tau. Interpretation of the pattern is difficult because there are six tau isoforms in normal brain and phosphorylation changes their mobility. By enzymatic dephosphorylation at high temperature, we have shifted the three abnormal bands obtained from dispersed PHFs to align with the six nonphosphorylated tau isoforms. By using antibodies specific for some of the inserts that distinguish the various isoforms and label PHFs, we have established a correspondence between PHFs, abnormal bands, and isoforms. This identification of isoforms is a necessary step in unravelling the molecular pathogenesis of PHFs.