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为推进慢性阻塞性肺疾病的治疗策略,必须揭示新的生物学机制。

Why new biology must be uncovered to advance therapeutic strategies for chronic obstructive pulmonary disease.

机构信息

Department of Cell Biology, Johns Hopkins School of Medicine, Baltimore, Maryland.

Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland.

出版信息

Am J Physiol Lung Cell Mol Physiol. 2021 Jan 1;320(1):L1-L11. doi: 10.1152/ajplung.00367.2020. Epub 2020 Nov 11.

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by the destruction of alveolar tissue (in emphysema) and airway remodeling (leading to chronic bronchitis), which cause difficulties in breathing. It is a growing public health concern with few therapeutic options that can reverse disease progression or mortality. This is in part because current treatments mainly focus on ameliorating symptoms induced by inflammatory pathways as opposed to curing disease. Hence, emerging research focused on upstream pathways are likely to be beneficial in the development of efficient therapeutics to address the root causes of disease. Some of these pathways include mitochondrial function, cytoskeletal structure and maintenance, and airway hydration, which are all affected by toxins that contribute to COPD. Because of the complexity of COPD and unknown targets for disease onset, simpler model organisms have proved to be useful tools in identifying disease-relevant pathways and targets. This review summarizes COPD pathology, current treatments, and therapeutic discovery research, with a focus on the aforementioned pathways that can advance the therapeutic landscape of COPD.

摘要

慢性阻塞性肺疾病(COPD)的特征是肺泡组织(肺气肿)和气道重塑(导致慢性支气管炎)的破坏,这导致呼吸困难。这是一个日益严重的公共卫生问题,治疗选择很少,无法逆转疾病进展或死亡率。部分原因是目前的治疗方法主要集中在改善炎症途径引起的症状,而不是治愈疾病。因此,关注上游途径的新兴研究可能有助于开发有效的治疗方法,以解决疾病的根本原因。其中一些途径包括线粒体功能、细胞骨架结构和维持以及气道水合作用,所有这些都受到导致 COPD 的毒素的影响。由于 COPD 的复杂性和疾病发作的未知靶点,较简单的模式生物已被证明是识别与疾病相关途径和靶点的有用工具。本综述总结了 COPD 的病理学、当前的治疗方法和治疗发现研究,重点介绍了上述可以推进 COPD 治疗领域的途径。

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