Hanger Diane P, Noble Wendy
Department of Neuroscience (P037), MRC Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
Int J Alzheimers Dis. 2011;2011:352805. doi: 10.4061/2011/352805. Epub 2011 Jul 11.
Tau is primarily a neuronal microtubule-associated protein that has functions related to the stabilisation of microtubules. Phosphorylation of tau is an important dynamic and regulatory element involved in the binding of tau to tubulin. Thus, highly phosphorylated tau is more likely to be present in the cytosolic compartment of neurons, whereas reduced phosphate burden allows tau to bind to and stabilise the microtubule cytoskeleton. Highly phosphorylated forms of tau are deposited in the brain in a range of neurodegenerative disorders including Alzheimer's disease, progressive supranuclear palsy, and frontotemporal lobar degeneration associated with Pick bodies. A key candidate kinase for both physiological and pathological tau phosphorylation is glycogen synthase kinase-3 (GSK-3). Multiple phosphorylation sites have been identified on tau exposed to GSK-3 in vitro and in cells. In this review, we highlight recent data suggesting a role for GSK-3 activity on physiological tau function and on tau dysfunction in neurodegenerative disease.
tau蛋白主要是一种与神经元微管相关的蛋白，具有与微管稳定相关的功能。tau蛋白的磷酸化是tau蛋白与微管蛋白结合所涉及的重要动态调节因素。因此，高度磷酸化的tau蛋白更有可能存在于神经元的胞质区室中，而磷酸盐负担的减轻则使tau蛋白能够结合并稳定微管细胞骨架。高度磷酸化形式的tau蛋白在一系列神经退行性疾病（包括阿尔茨海默病、进行性核上性麻痹以及与Pick小体相关的额颞叶痴呆）的大脑中沉积。糖原合酶激酶-3（GSK-3）是生理和病理tau蛋白磷酸化的关键候选激酶。在体外和细胞中，已在暴露于GSK-3的tau蛋白上鉴定出多个磷酸化位点。在本综述中，我们重点介绍了近期的数据，这些数据表明GSK-3活性在生理tau蛋白功能以及神经退行性疾病中tau蛋白功能障碍方面发挥作用。
