Department of Biochemistry and Molecular Biology/Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
Autophagy. 2012 Jan;8(1):142-3. doi: 10.4161/auto.8.1.18536. Epub 2012 Jan 1.
The target of rapamycin (TOR) kinase is part of an evolutionarily conserved signaling pathway that coordinates cell growth, survival, and autophagy. Previously, pharmacological studies using rapamycin have suggested a cardioprotective effect of TOR signaling inhibition on cardiomyopathy. We found that rapamycin exerts a conserved cardioprotective effect in two adult zebrafish models of cardiomyopathy of different etiology, and provided the first genetic evidence to support a long-term cardioprotective effect of TOR signaling inhibition. Moreover, we detected dynamic TOR-autophagy activities along different stages of cardiomyopathy. This needs to be considered when developing TOR-autophagy-based therapeutics for cardiomyopathy.
雷帕霉素（TOR）激酶是进化保守信号通路的一部分，该通路协调细胞生长、存活和自噬。先前使用雷帕霉素的药理学研究表明，TOR 信号抑制对心肌病具有心脏保护作用。我们发现雷帕霉素在两种不同病因的成年斑马鱼心肌病模型中发挥了保守的心脏保护作用，并提供了第一个遗传证据支持 TOR 信号抑制的长期心脏保护作用。此外，我们还检测到在心肌病的不同阶段TOR-自噬活性的动态变化。在开发基于 TOR-自噬的心肌病治疗方法时需要考虑这一点。
