The role of phosphorylation reaction of tau factor in ischemic neuronal cell death

Tau因子是由磷酸化反应调控的细胞骨架蛋白。近年来，高磷酸化的tau因子被认为参与了阿尔茨海默病的发病机制。我们检测了短暂性前脑缺血后海马中tau因子的磷酸化状态。serin199/202在CA1亚区出现了短暂的高磷酸化，而serin396的磷酸化没有发生变化。此外，我们通过位点定向诱变与TAT蛋白联合制备了199/202去磷酸化的form-tau因子。脑室内注射这种去磷酸化形式的tau蛋白可以防止缺血性神经元细胞死亡，而正常形式的tau蛋白则没有。由此可见，丝氨酸199/202的过度磷酸化在短暂性缺血后神经元细胞死亡中起重要作用。

Tau factor is cytoskeletal protein, which regulated by phosphorylation reaction. Recently, hyperphosphorylated tau factor is known to be involved in the mechanism of Alzheimer Disease. We examined the phosphorylation state of tau factor in the hippocampus after transient forebrain ischemia. The hyperphosphorylation of serin199/202 was transiently found in CA1 subfield, while the phosphorylation of serin396 did not change. Furthermore, we prepared 199/202-dephosphorylated form-tau factor by the site directed mutagenesis combined with TAT protein. Intraventricle injection of this dephosphorylated form-tau prevented ischemic neuronal cell death, while normal form-tau did not. It is concluded that the hyperphosphorylation of serin199/202 play an important role for neuronal cell death after transient ischemia.