Department of Molecular Medicine and Medical Biotechnology, Medical School, University of Naples Federico II, Via S. Pansini n. 5, 80131 Naples, Italy.
Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Via Delpino 1, 80137 Naples, Italy.
Int J Mol Sci. 2022 Aug 13;23(16):9089. doi: 10.3390/ijms23169089.
Cathepsins encompass a family of lysosomal proteases that mediate protein degradation and turnover. Although mainly localized in the endolysosomal compartment, cathepsins are also found in the cytoplasm, nucleus, and extracellular space, where they are involved in cell signaling, extracellular matrix assembly/disassembly, and protein processing and trafficking through the plasma and nuclear membrane and between intracellular organelles. Ubiquitously expressed in the body, cathepsins play regulatory roles in a wide range of physiological processes including coagulation, hormone secretion, immune responses, and others. A dysregulation of cathepsin expression and/or activity has been associated with many human diseases, including cancer, diabetes, obesity, cardiovascular and inflammatory diseases, kidney dysfunctions, and neurodegenerative disorders, as well as infectious diseases. In viral infections, cathepsins may promote (1) activation of the viral attachment glycoproteins and entry of the virus into target cells; (2) antigen processing and presentation, enabling the virus to replicate in infected cells; (3) up-regulation and processing of heparanase that facilitates the release of viral progeny and the spread of infection; and (4) activation of cell death that may either favor viral clearance or assist viral propagation. In this review, we report the most relevant findings on the molecular mechanisms underlying cathepsin involvement in viral infection physiopathology, and we discuss the potential of cathepsin inhibitors for therapeutical applications in viral infectious diseases.
组织蛋白酶包含一个溶酶体蛋白酶家族，介导蛋白质降解和周转。虽然主要定位于内溶酶体区室，但组织蛋白酶也存在于细胞质、核和细胞外空间，在那里它们参与细胞信号转导、细胞外基质的组装/拆卸以及蛋白质通过质膜和核膜的加工和运输以及细胞内细胞器之间的运输。组织蛋白酶在体内广泛表达，在包括凝血、激素分泌、免疫反应等在内的多种生理过程中发挥调节作用。组织蛋白酶表达和/或活性的失调与许多人类疾病有关，包括癌症、糖尿病、肥胖症、心血管和炎症性疾病、肾功能障碍和神经退行性疾病以及传染病。在病毒感染中，组织蛋白酶可能促进（1）病毒附着糖蛋白的激活和病毒进入靶细胞；（2）抗原加工和呈递，使病毒在感染细胞中复制；（3）上调和加工肝素酶，促进病毒产物的释放和感染的传播；以及（4）细胞死亡的激活，这可能有利于病毒清除或有助于病毒增殖。在这篇综述中，我们报告了组织蛋白酶参与病毒感染病理生理学的分子机制的最相关发现，并讨论了组织蛋白酶抑制剂在病毒感染性疾病治疗中的应用潜力。
