Hanger Diane P, Anderton Brian H, Noble Wendy
MRC Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK.
Trends Mol Med. 2009 Mar;15(3):112-9. doi: 10.1016/j.molmed.2009.01.003. Epub 2009 Feb 24.
The microtubule-associated protein tau is integral to the pathogenesis of Alzheimer's disease (AD), as well as several related disorders, termed tauopathies, in which tau is deposited in affected brain regions. In the tauopathies, pathological tau is in an elevated state of phosphorylation and is aberrantly cleaved. It also exhibits abnormal conformations and becomes aggregated, resulting in neurofibrillary tau pathology. Recent evidence suggests that relatively early disease-associated changes in soluble tau proteins, including phosphorylation, are involved in the induction of neuronal death. Here, we summarize recent developments that suggest new therapeutic strategies to prevent or reduce the progression of pathology in the tauopathies. A list of tau phosphorylation sites identified in the tauopathies and in controls accompanies this review.
微管相关蛋白tau对于阿尔茨海默病（AD）以及几种相关疾病（称为tau蛋白病）的发病机制至关重要，在这些疾病中，tau蛋白沉积在受影响的脑区。在tau蛋白病中，病理性tau蛋白处于磷酸化水平升高且异常裂解的状态。它还表现出异常构象并发生聚集，导致神经原纤维tau蛋白病变。最近的证据表明，可溶性tau蛋白中与疾病相关的相对早期变化，包括磷酸化，参与了神经元死亡的诱导。在此，我们总结了近期的进展，这些进展提示了预防或减少tau蛋白病病理进展的新治疗策略。本综述附有在tau蛋白病和对照中鉴定出的tau蛋白磷酸化位点列表。
