Lim Jeong-A, Meena Naresh Kumar, Raben Nina
Division of Medical Genetics, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
Ann Transl Med. 2019 Jul;7(13):279. doi: 10.21037/atm.2019.03.51.
Autophagy is a major intracellular self-digestion process that brings cytoplasmic materials to the lysosome for degradation. Defective autophagy has been linked to a broad range of human disorders, including cancer, diabetes, neurodegeneration, autoimmunity, cardiovascular diseases, and myopathies. In Pompe disease, a severe neuromuscular disorder, disturbances in autophagic process manifest themselves as progressive accumulation of undegraded cellular debris in the diseased muscle cells. A growing body of evidence has connected this defect to the decline in muscle function and muscle resistance to the currently available treatment-enzyme replacement therapy (ERT). Both induction and inhibition of autophagy have been tested in pre-clinical studies in a mouse model of the disease. Here, we discuss strengths and weaknesses of different approaches to address autophagic dysfunction in the context of Pompe disease.
自噬是一种主要的细胞内自我消化过程，它将细胞质物质运送到溶酶体进行降解。自噬功能缺陷与多种人类疾病有关，包括癌症、糖尿病、神经退行性疾病、自身免疫性疾病、心血管疾病和肌病。在庞贝病（一种严重的神经肌肉疾病）中，自噬过程的紊乱表现为患病肌肉细胞中未降解的细胞碎片逐渐积累。越来越多的证据表明，这种缺陷与肌肉功能下降以及肌肉对目前可用的治疗方法——酶替代疗法（ERT）的抵抗力下降有关。在该疾病的小鼠模型的临床前研究中，已经对自噬的诱导和抑制进行了测试。在此，我们讨论在庞贝病背景下解决自噬功能障碍的不同方法的优缺点。
