Autism is characterized by repetitive behaviors, impaired social interactions, and communication deficits. It is a prevalent neurodevelopmental disorder, and available treatments offer little benefit. Here, we show that genetically reducing the protein tau prevents behavioral signs of autism in two mouse models simulating distinct causes of this condition. Similar to a proportion of people with autism, both models have epilepsy, abnormally enlarged brains, and overactivation of the phosphatidylinositol 3-kinase (PI3K)/Akt (protein kinase B)/ mammalian target of rapamycin (mTOR) signaling pathway. All of these abnormalities were prevented or markedly diminished by partial or complete genetic removal of tau. We identify disinhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a negative PI3K regulator that tau controls, as a plausible mechanism and demonstrate that tau interacts with PTEN via tau's proline-rich domain. Our findings suggest an enabling role of tau in the pathogenesis of autism and identify tau reduction as a potential therapeutic strategy for some of the disorders that cause this condition.

中文翻译：

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减少Tau可以防止老鼠模型中自闭症的关键特征。

自闭症的特征是行为重复，社交互动受损和沟通不足。它是一种普遍的神经发育障碍，可用的治疗方法几乎没有益处。在这里，我们显示出遗传降低蛋白质tau可以防止在模拟这种情况的不同原因的两个小鼠模型中自闭症的行为迹象。与部分自闭症患者相似，这两种模型都患有癫痫症，大脑异常扩大以及磷脂酰肌醇3-激酶（PI3K）/ Akt（蛋白激酶B）/雷帕霉素哺乳动物靶标（mTOR）信号通路过度活化。通过部分或完全遗传去除tau可以预防或显着减少所有这些异常。我们确定了10号染色体（PTEN）（tau控制的PI3K负调节剂）上缺失的磷酸酶和张力蛋白同源物的抑制作用，作为可能的机制，并证明tau通过tau富含脯氨酸的结构域与PTEN相互作用。我们的研究结果表明tau在自闭症发病机理中具有促成作用，并将tau降低确定为引起该病的某些疾病的潜在治疗策略。