Tau蛋白在神经元细胞质和细胞核内的不同功能及其磷酸化对阿兹海默病的影响

The different functions of Tau protein in the cytoplasm and nucleus of neuron and the effect of its phosphorylation on Alzheimer's Disease

Tau蛋白的功能,现有的研究结果已经比较清晰,涉及多种胞内异常,包括自噬、轴质运输、神经极性的紊乱,以及胞质Tau蛋白分泌到胞外所引起的一系列变化。Tau蛋白在细胞质和细胞核内具有不同功能,在胞质中以微管相关蛋白(microtubule-associated proteins,MAPs)形式承担运输、细胞支架和细胞运动等功能;在核内大量存在于核仁中,并作为端粒成分保护核内DNA;糖原合酶激酶-3(glycogen synthase kinase-3,GSK-3)、磷酸腺苷活化蛋白激酶(adenosine-monophosphate activated protein kinase,AMPK)、微管亲和调节蛋白激酶(microtubule-affinity regulating kinases,MARKs)和腺苷酸环化酶依赖的蛋白激酶(cyclic AMP-dependent protein kinase,PKA)对Tau蛋白异常磷酸化的影响,并由此讨论Tau蛋白在老年痴呆等神经退行性疾病中的可能作用。

Current researches have drawn clear conclusions on the functions of Tau protein, which involve various intracellular anomalies including autophagy, axoplasmic transport and disorders of neural polarity, and a series of changes caused by secreted Tau protein. Tau has different roles in the cytoplasm and the nucleus. As microtubule-associated protein （MAP） in the cytoplasm, it plays a part as cytoskeleton and also in cellular transportation and movement; while in the nucleus, it is abundant in the nucleolus and protects nuclear DNA as a telomere component. The effect of a variety of kinases on the abnormal phosphorylation of Tau is reviewed, including glycogen synthase kinase-3 （ GSK-3）, adenosine-monophosphate activated protein kinase （ AMPK）, microtubule-affinity regulating kinases （ MARK）, and cyclic AMP-dependent protein kinase （ PKA）. The possible role of Tau in neurodegenerative disorders such as Alzheimerg Disease （AD） is then discussed.