Mandelkow E M, Mandelkow E
Max-Planck-Unit for Structural Molecular Biology, Hamburg, Germany.
Trends Cell Biol. 1998 Nov;8(11):425-7. doi: 10.1016/s0962-8924(98)01368-3.
Neurofibrillar protein aggregates containing tau are one of the major hallmarks of Alzheimer's disease (AD). In normal cells, tau stabilizes axonal microtubules, which are the tracks for intracellular traffic. In AD, tau becomes abnormally phosphorylated, aggregates into paired helical filaments and loses its ability to maintain the microtubule tracks. There is renewed interest in tau as a causative factor in neurodegenerative disease based on recently discovered mutations in the gene encoding tau. This article discusses how changes in tau protein could lead to retraction of neuronal processes and thus cell death and argues that tau pathology, rather than beta-amyloid, might be the most reliable indicative factor for AD.
含有tau蛋白的神经原纤维蛋白聚集体是阿尔茨海默病（AD）的主要标志之一。在正常细胞中，tau蛋白可稳定轴突微管，而轴突微管是细胞内物质运输的轨道。在AD中，tau蛋白发生异常磷酸化，聚集成双螺旋丝，失去维持微管轨道的能力。基于最近在编码tau蛋白的基因中发现的突变，tau蛋白作为神经退行性疾病的致病因素重新引起了人们的关注。本文讨论了tau蛋白的变化如何导致神经元突起回缩，进而导致细胞死亡，并认为tau蛋白病变而非β-淀粉样蛋白可能是AD最可靠的指示因素。
