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

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY Fundamental & Clinical Pharmacology Pub Date : 2023-08-23 DOI:10.1111/fcp.12946

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

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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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人类中性粒细胞弹性蛋白酶抑制剂：分类、生物合成来源及其与相关疾病的关联性。

背景：人中性粒细胞弹性蛋白酶是一种多功能蛋白酶，其功能是打破蛋白质的键，将其降解为多肽或氨基酸。此外，它在抵抗细菌感染的免疫机制中发挥着重要作用，是组织重塑和炎症的关键介质。然而，当这种酶的细胞外释放因其生理抑制剂的低水平而失调时，最终会导致蛋白质降解，特别是弹性蛋白以及细胞外基质的其他成分，对上皮细胞造成损伤，从而促进持续性炎症并影响先天性免疫系统，并因此成为严重炎症性疾病，特别是与心肺系统相关疾病的发病基础：本综述旨在提供有关合成或生物来源的几种分子的弹性蛋白酶抑制特性的最新信息，以及它们在相关病症中的分类和相关性，因为清楚地了解这些分子的功能与这种蛋白酶的抑制能力，可以为开发药物疗法提供有价值的信息，从而改变各种炎症性疾病的预后和存活率：从科学数据库中收集数据，包括 PubMed、Google Scholar、Science Direct、Nature、Wiley、Scopus 和 Scielo。结果：我们审查并收录了 132 篇文章：我们审查并收录了 132 篇关于中性粒细胞弹性蛋白酶活性和已知抑制剂的概念性文章：结论：根据弹性蛋白酶抑制剂的动力学行为、结构-功能关系、化学性质、起源、药效学和实验进展等特定方面了解弹性蛋白酶抑制剂的作用机制，可对 HNE 抑制剂进行广泛分类。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fundamental & Clinical Pharmacology 医学-药学

CiteScore

5.30

自引率

6.90%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.