Goedert M, Spillantini M G, Crowther R A
Medical Research Council Laboratory of Molecular Biology, Cambridge, U.K.
Brain Pathol. 1991 Jul;1(4):279-86. doi: 10.1111/j.1750-3639.1991.tb00671.x.
The paired helical filament is the major fibrous component of neurofibrillary pathology in Alzheimer's disease. Over the last three years evidence has accumulated that the microtubule-associated protein tau forms an important, if not the sole, constituent of the paired helical filament. Tau protein in normal brain is bound to axonal microtubules by a tandem repeat region. In Alzheimer's disease a proportion of tau protein becomes abnormally phosphorylated and is no longer associated with axonal microtubules but instead accumulates in paired helical filaments throughout affected nerve cells. The tandem repeat region contributes substantially to the structural core of the paired helical filament, around which the amino-terminal half of the molecule forms a disordered coat.
双螺旋丝是阿尔茨海默病神经原纤维病变的主要纤维成分。在过去三年中,越来越多的证据表明,微管相关蛋白tau即便不是双螺旋丝的唯一成分,也是其重要组成部分。正常大脑中的tau蛋白通过串联重复区域与轴突微管结合。在阿尔茨海默病中,一部分tau蛋白发生异常磷酸化,不再与轴突微管相关联,而是在整个受影响的神经细胞中积累成双螺旋丝。串联重复区域对双螺旋丝的结构核心有很大贡献,分子的氨基末端一半围绕该核心形成无序的外壳。