Vafai Scott B, Stock Jeffry B
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
FEBS Lett. 2002 May 8;518(1-3):1-4. doi: 10.1016/s0014-5793(02)02702-3.
Tau hyperphosphorylation is a central event in the development of Alzheimer's Disease (AD). Protein phosphatase 2A (PP2A) heterotrimer formation is necessary for efficient dephosphorylation of the tau protein. S-Adenosylmethionine-dependent carboxyl methylation is essential for the assembly of PP2A heterotrimers. Epidemiological evidence indicates that elevated plasma homocysteine is an independent risk factor for AD. Homocysteine is a key intermediate in the methyl cycle and elevated plasma homocysteine results in a global decrease in cellular methylation. We propose that the PP2A methylation system is the link relating elevated plasma homocysteine to AD.
tau蛋白过度磷酸化是阿尔茨海默病（AD）发展过程中的核心事件。蛋白磷酸酶2A（PP2A）异源三聚体的形成是tau蛋白有效去磷酸化所必需的。依赖S-腺苷甲硫氨酸的羧基甲基化对于PP2A异源三聚体的组装至关重要。流行病学证据表明，血浆同型半胱氨酸水平升高是AD的一个独立危险因素。同型半胱氨酸是甲基循环中的关键中间体，血浆同型半胱氨酸水平升高会导致细胞甲基化整体减少。我们认为，PP2A甲基化系统是将血浆同型半胱氨酸水平升高与AD联系起来的纽带。
