A variety of findings from in vitro experiments and animal models support the hypothesis that one contribution to pathogenesis in Alzheimer's disease (AD) is enhanced phosphorylation of tau protein, which may be triggered by amyloid β (Aβ) and mediated by impaired activity of the PI3K/Akt signaling pathway. A number of tyrosine phosphatases act to reduce PI3K/Akt activity, and inhibition of tyrosine phosphatases is protective against Aβ toxicity in cell cultures and whole animals. Results from analysis of exome sequenced late onset AD cases and controls similarly show that rare coding variants predicted to damage PI3K functioning increase AD risk, whereas those which are predicted to damage genes for tyrosine phosphatase genes are protective. Taken together, these results support the proposition that tyrosine phosphatase antagonists might be trialed as therapeutic agents to protect against the development of AD.

中文翻译：

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小型综述：PI3K/Akt 通路和酪氨酸磷酸酶在阿尔茨海默病易感性中的作用

体外实验和动物模型的各种发现支持这样一种假设，即阿尔茨海默病 (AD) 发病机制的一个原因是 tau 蛋白磷酸化增强，这可能由淀粉样蛋白 β (Aβ) 触发并由 PI3K 活性受损介导/Akt 信号通路。许多酪氨酸磷酸酶可降低 PI3K/Akt 活性，抑制酪氨酸磷酸酶可防止细胞培养物和整个动物中的 Aβ 毒性。外显子组测序的晚发性 AD 病例和对照的分析结果类似地表明，预测会损害 PI3K 功能的稀有编码变体会增加 AD 风险，而那些预测会损害酪氨酸磷酸酶基因的基因则具有保护作用。综合起来，