Kosik K S
Department of Neurology (Neuroscience), Harvard Medical School, Boston, MA.
Mol Neurobiol. 1990 Fall-Winter;4(3-4):171-9. doi: 10.1007/BF02780339.
Many of the human neurodegenerative conditions involve a reorganization of the neuronal cytoskeleton. The way in which the cytoskeleton is reorganized may provide a clue to the nature of the insult causing the neurodegeneration. The most common of these conditions is Alzheimer's disease, in which microtubules are lost from neurites that fill up with filamentous structures. One component of the filamentous structures is the microtubule-associated protein (MAP), tau. The tau protein is the product of a single gene expressed predominantly in neurons. The tau gene undergoes complex alternative splicing that is regulated both by development, and by the particular neuronal cell population in which it is expressed. Tau protein can be further modified, following its translation by phosphorylation at several sites. Much of the recent interest in the transition of tau to an abnormal state within a tangle-bearing neuron has focused on phosphorylation. A group of proteins that migrate slightly more slowly than tau, designated PHF-tau, are found in regions of the Alzheimer brain rich in dystrophic neurites, are hyperphosphorylated, fail to bind to microtubules, have distinct solubility properties, and can be derived from fractions of paired helical filaments (PHF).
许多人类神经退行性疾病都涉及神经元细胞骨架的重组。细胞骨架重组的方式可能为导致神经退行性变的损伤性质提供线索。其中最常见的疾病是阿尔茨海默病，在该病中，神经突中的微管丢失，神经突中充满了丝状结构。丝状结构的一个组成部分是微管相关蛋白（MAP），即tau蛋白。tau蛋白是一个主要在神经元中表达的单基因的产物。tau基因经历复杂的可变剪接，其受发育以及它所表达的特定神经元细胞群体的调控。tau蛋白在翻译后可在多个位点通过磷酸化进一步修饰。最近，许多关于tau蛋白在含有神经缠结的神经元内转变为异常状态的研究都集中在磷酸化上。一组迁移速度比tau蛋白略慢的蛋白质，称为PHF-tau，在富含营养不良性神经突的阿尔茨海默病大脑区域中被发现，它们高度磷酸化，无法与微管结合，具有独特的溶解性，并且可以从成对螺旋丝（PHF）组分中获得。
