Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Elgomhourya street, Mansoura, 36551, Egypt.
Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Neurotox Res. 2019 May;35(4):987-992. doi: 10.1007/s12640-018-9974-3. Epub 2018 Oct 25.
Tauopathy is a pathological hallmark of many neurodegenerative diseases. It is characterized by abnormal aggregates of pathological phosphotau and somatodendritic redistribution. One suggested strategy for treating tauopathy is to stimulate autophagy, hence, getting rid of these pathological protein aggregates. One key controller of autophagy is mTOR. Since stimulation of mTOR leads to inhibition of autophagy, inhibitors of mTOR will cause stimulation of autophagy process. In this report, tauopathy was induced in mice using annonacin. Blocking of mTOR was achieved through stereotaxic injection of siRNA against mTOR. The behavioral and immunohistochemical evaluation revealed the development of tauopathy model as proven by deterioration of behavioral performance in open field test and significant tau aggregates in annonacin-treated mice. Blocking of mTOR revealed significant clearance of tau aggregates in the injected side; however, tau expression was not affected by mTOR blockage.
tau 病是许多神经退行性疾病的病理特征。其特征在于病理性磷酸化 tau 的异常聚集和树突状分布。一种治疗 tau 病的建议策略是刺激自噬，从而清除这些病理性蛋白聚集体。自噬的一个关键控制器是 mTOR。由于 mTOR 的刺激会导致自噬的抑制，因此 mTOR 的抑制剂会引起自噬过程的刺激。在本报告中，使用 annonacin 在小鼠中诱导 tau 病。通过立体定向注射 mTOR 的 siRNA 来实现 mTOR 的阻断。行为学和免疫组织化学评估显示 tau 病模型的发展，正如在开放场测试中行为表现恶化以及 annonacin 处理的小鼠中存在明显的 tau 聚集所证明的那样。mTOR 的阻断显示出 tau 聚集体在注射侧的显著清除；然而，mTOR 阻断对 tau 表达没有影响。
