Sandri Angela, Boschi Federico
Department of Diagnostics and Public Health, University of Verona, Strada Le Grazie 8-15, 37134 Verona, Italy.
General and Upper GI Surgery Division, Azienda Ospedaliera Universitaria Integrata Verona, Piazzale Stefani 1, 37126 Verona, Italy.
Int J Mol Sci. 2025 Feb 21;26(5):1871. doi: 10.3390/ijms26051871.
Cystic fibrosis (CF) is characterized by chronic respiratory infections and excessive inflammation, driven by both host- and pathogen-derived proteases. The dysregulated activity of proteolytic enzymes such as neutrophil elastase (NE), cathepsin G, and matrix metalloproteases (MMPs) degrades lung tissue, exacerbates airway remodeling, and perpetuates inflammatory cycles. Concurrently, bacterial proteases from pathogens such as and contribute to immune evasion and tissue destruction, compounding disease severity. Despite advances in antimicrobial and anti-inflammatory therapies, protease-driven lung damage remains a critical challenge. This review examines the dual role of host and bacterial proteases in CF pathophysiology, highlighting emerging protease-targeted therapies aimed at mitigating lung damage and inflammation. Strategies explored include the inhibition of NE, MMPs, and bacterial proteases, with a focus on innovative therapeutic approaches such as dual-function inhibitors, biologics, and advanced drug delivery systems. By restoring the protease-antiprotease balance, these interventions offer the potential to improve clinical outcomes and quality of life for CF patients.
囊性纤维化（CF）的特征是慢性呼吸道感染和过度炎症，这是由宿主和病原体衍生的蛋白酶共同驱动的。诸如中性粒细胞弹性蛋白酶（NE）、组织蛋白酶G和基质金属蛋白酶（MMPs）等蛋白水解酶的活性失调会降解肺组织，加剧气道重塑，并使炎症循环持续存在。同时，来自诸如[此处原文缺失具体病原体名称]等病原体的细菌蛋白酶会导致免疫逃逸和组织破坏，加重疾病严重程度。尽管在抗菌和抗炎治疗方面取得了进展，但蛋白酶驱动的肺损伤仍然是一个关键挑战。本综述探讨了宿主和细菌蛋白酶在CF病理生理学中的双重作用，重点介绍了旨在减轻肺损伤和炎症的新兴蛋白酶靶向治疗方法。探索的策略包括抑制NE、MMPs和细菌蛋白酶，重点关注双功能抑制剂、生物制剂和先进药物递送系统等创新治疗方法。通过恢复蛋白酶 - 抗蛋白酶平衡，这些干预措施有可能改善CF患者的临床结局和生活质量。
