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Human neutrophil elastase inhibitors: Classification, biological‐synthetic sources and their relevance in related diseases

弹性蛋白酶 免疫系统 先天免疫系统 炎症 功能(生物学) 中性粒细胞弹性蛋白酶 中性粒细胞胞外陷阱 计算生物学 生物 生物化学 化学 细胞生物学 免疫学
作者
Jhonnatan Styver Ocampo‐Gallego,David Pedroza‐Escobar,Ana Ruth Caicedo‐Ortega,María Teresa Berumen‐Murra,Ana Lucía Novelo‐Aguirre,Rebeca Denis de Sotelo‐León,Dealmy Delgadillo‐Guzmán
出处
期刊:Fundamental & Clinical Pharmacology [Wiley]
卷期号:38 (1): 13-32 被引量:5
标识
DOI:10.1111/fcp.12946
摘要

Abstract Background Human neutrophil elastase is a multifunctional protease enzyme whose function is to break the bonds of proteins and degrade them to polypeptides or amino acids. In addition, it plays an essential role in the immune mechanism against bacterial infections and represents a key mediator in tissue remodeling and inflammation. However, when the extracellular release of this enzyme is dysregulated in response to low levels of its physiological inhibitors, it ultimately leads to the degradation of proteins, in particular elastin, as well as other components of the extracellular matrix, producing injury to epithelial cells, which can promote sustained inflammation and affect the innate immune system, and, therefore, be the basis for the development of severe inflammatory diseases, especially those associated with the cardiopulmonary system. Objective This review aims to provide an update on the elastase inhibitory properties of several molecules, either synthetic or biological sources, as well as their classification and relevance in related pathologies since a clear understanding of the function of these molecules with the inhibitory capacity of this protease can provide valuable information for the development of pharmacological therapies that manage to modify the prognosis and survival of various inflammatory diseases. Methods Collected data from scientific databases, including PubMed, Google Scholar, Science Direct, Nature, Wiley, Scopus, and Scielo. Articles published in any country and language were included. Results We reviewed and included 132 articles conceptualizing neutrophil elastase activity and known inhibitors. Conclusion Understanding the mechanism of action of elastase inhibitors based on particular aspects such as their kinetic behavior, structure–function relationship, chemical properties, origin, pharmacodynamics, and experimental progress has allowed for a broad classification of HNE inhibitors.
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