Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, 16 Medical Drive, 117600, Singapore.
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 2 Medical Drive, 117597, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, 117456, Singapore.
Pharmacol Res. 2019 Jun;144:1-7. doi: 10.1016/j.phrs.2019.04.005. Epub 2019 Apr 3.
Autophagy is an evolutionary conserved process that is responsible for maintaining cellular homeostasis through lysosome-dependent degradation of damaged proteins, lipid and organelles. When autophagy is dysregulated by factors such as cigarette smoking, environmental insults and ageing, it can lead to formation of aggresome-bodies and enhanced production of reactive oxygen species (ROS), of which contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD). This review will aim to decipher the pathogenic process of autophagy that is dysregulated by the various risk factors of COPD, leading to either cell death or senescence and COPD progression. It will also cover potential therapeutics that can be used to augment autophagy for the treatment of COPD. This will help shed light on COPD pathophysiology in the context of autophagy so that novel therapeutics can be developed to provide target-specific treatment.
自噬是一种进化上保守的过程，通过溶酶体依赖性降解受损蛋白质、脂质和细胞器来维持细胞内稳态。当自噬受到香烟烟雾、环境损伤和衰老等因素的失调调节时，它会导致聚集体的形成和活性氧（ROS）的产生增加，这有助于慢性阻塞性肺疾病（COPD）的发病机制。本综述旨在解析由 COPD 的各种危险因素失调的自噬的发病机制，导致细胞死亡或衰老和 COPD 的进展。它还将涵盖可用于增强自噬治疗 COPD 的潜在治疗方法。这将有助于阐明自噬背景下 COPD 的病理生理学，从而开发出针对特定靶点的新型治疗方法。
