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

Author:

Ocampo‐Gallego Jhonnatan Styver1,Pedroza‐Escobar David2ORCID,Caicedo‐Ortega Ana Ruth3,Berumen‐Murra María Teresa1,Novelo‐Aguirre Ana Lucía1,de Sotelo‐León Rebeca Denis4,Delgadillo‐Guzmán Dealmy1ORCID

Affiliation:

1. Departamento de Farmacologia, Facultad de Medicina UT Universidad Autonoma de Coahuila Torreon Mexico

2. Departamento de Bioquimica, Centro de Investigacion Biomedica Universidad Autonoma de Coahuila Torreon Mexico

3. Departamento de Quimica, Facultad de Ciencias Universidad Nacional de Colombia Bogota Colombia

4. Departmento de Nutricion. Unidad de Medicina Familiar, UMAA 53 Instituto Mexicano del Seguro Social Durango Mexico

Abstract

AbstractBackgroundHuman 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.ObjectiveThis 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.MethodsCollected data from scientific databases, including PubMed, Google Scholar, Science Direct, Nature, Wiley, Scopus, and Scielo. Articles published in any country and language were included.ResultsWe reviewed and included 132 articles conceptualizing neutrophil elastase activity and known inhibitors.ConclusionUnderstanding 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.

Publisher

Wiley

Subject

Pharmacology (medical),Pharmacology

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