INSERM UMR-1100, Centre d'Etude des Pathologies Respiratoires and Université de Tours, 37032 Tours, France.
Faculty of Chemistry, University of Gdansk, 80-398 Gdansk, Poland.
J Med Chem. 2020 Nov 25;63(22):13258-13265. doi: 10.1021/acs.jmedchem.0c00776. Epub 2020 Aug 7.
Cathepsin C (CatC) is a cysteine dipeptidyl aminopeptidase that activates most of tissue-degrading elastase-related serine proteases. Thus, CatC appears as a potential therapeutic target to impair protease-driven tissue degradation in chronic inflammatory and autoimmune diseases. A depletion of proinflammatory elastase-related proteases in neutrophils is observed in patients with CatC deficiency (Papillon-Lefèvre syndrome). To address and counterbalance unwanted effects of elastase-related proteases, chemical inhibitors of CatC are being evaluated in preclinical and clinical trials. Neutrophils may contribute to the diffuse alveolar inflammation seen in acute respiratory distress syndrome (ARDS) which is currently a growing challenge for intensive care units due to the outbreak of the COVID-19 pandemic. Elimination of elastase-related neutrophil proteases may reduce the progression of lung injury in these patients. Pharmacological CatC inhibition could be a potential therapeutic strategy to prevent the irreversible pulmonary failure threatening the life of COVID-19 patients.
组织蛋白酶 C（CatC）是一种半胱氨酸二肽基氨肽酶，可激活大多数组织降解的丝氨酸蛋白酶相关弹性酶。因此，CatC 似乎是一种潜在的治疗靶点，可以削弱慢性炎症和自身免疫性疾病中蛋白酶驱动的组织降解。在 CatC 缺乏症（Papillon-Lefèvre 综合征）患者的中性粒细胞中观察到促炎弹性酶相关蛋白酶的耗竭。为了应对和抵消弹性酶相关蛋白酶的不良影响，正在临床前和临床试验中评估 CatC 的化学抑制剂。中性粒细胞可能导致急性呼吸窘迫综合征（ARDS）中弥漫性肺泡炎症，由于 COVID-19 大流行，ARDS 目前对重症监护病房构成了越来越大的挑战。消除与弹性酶相关的中性粒细胞蛋白酶可能会减少这些患者肺损伤的进展。药理学 CatC 抑制可能是预防威胁 COVID-19 患者生命的不可逆性肺衰竭的潜在治疗策略。
