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1.
Mol Aspects Med ; 88: 101150, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36283280

RESUMO

Biomedical research often focuses on properties that differentiate between diseased and healthy tissue; one of the current focuses is elevated expression and altered localisation of proteases. Among these proteases, dysregulation of cysteine cathepsins can frequently be observed in inflammation-associated diseases, which tips the functional balance from normal physiological to pathological manifestations. Their overexpression and secretion regularly exhibit a strong correlation with the development and progression of such diseases, making them attractive pharmacological targets. But beyond their mostly detrimental role in inflammation-associated diseases, cysteine cathepsins are physiologically highly important enzymes involved in various biological processes crucial for maintaining homeostasis and responding to different stimuli. Consequently, several challenges have emerged during the efforts made to translate basic research data into clinical applications. In this review, we present both physiological and pathological roles of cysteine cathepsins and discuss the clinical potential of cysteine cathepsin-targeting strategies for disease management and diagnosis.


Assuntos
Catepsinas , Cisteína , Humanos , Catepsinas/metabolismo , Cisteína/metabolismo , Inflamação/patologia
2.
Expert Opin Ther Targets ; 24(6): 573-588, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32228244

RESUMO

Introduction: Cysteine cathepsins are involved in the development and progression of numerous inflammation-associated diseases such as cancer, arthritis, bone and immune disorders. Consequently, there is a drive to progress research efforts focused on cathepsin use in diagnostics and as therapeutic targets in disease.Areas covered: This review discusses the potential of cysteine cathepsins as therapeutic targets in inflammation-associated diseases and recent advances in preclinical and clinical research. We describe direct targeting of cathepsins for treatment purposes and their indirect use in diagnostics.Expert opinion: The targeting of cysteine cathepsins has not translated into the clinic; this failure is attributed to off- and on-target side effects and/or the lack of companion biomarkers. This field now embraces developments in diagnostic imaging, the activation of prodrugs and antibody-drug conjugates for targeted drug delivery. The future lies in improved molecular tools and therapeutic concepts that will find a wide spectrum of uses in diagnostic and therapeutic applications.


Assuntos
Catepsinas/metabolismo , Inflamação/tratamento farmacológico , Terapia de Alvo Molecular , Animais , Cisteína/metabolismo , Diagnóstico por Imagem/métodos , Sistemas de Liberação de Medicamentos , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/farmacologia , Inflamação/diagnóstico , Inflamação/patologia , Pró-Fármacos
3.
Cells ; 8(3)2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30897858

RESUMO

: For a long time, cysteine cathepsins were considered primarily as proteases crucial for nonspecific bulk proteolysis in the endolysosomal system. However, this view has dramatically changed, and cathepsins are now considered key players in many important physiological processes, including in diseases like cancer, rheumatoid arthritis, and various inflammatory diseases. Cathepsins are emerging as important players in the extracellular space, and the paradigm is shifting from the degrading enzymes to the enzymes that can also specifically modify extracellular proteins. In pathological conditions, the activity of cathepsins is often dysregulated, resulting in their overexpression and secretion into the extracellular space. This is typically observed in cancer and inflammation, and cathepsins are therefore considered valuable diagnostic and therapeutic targets. In particular, the investigation of limited proteolysis by cathepsins in the extracellular space is opening numerous possibilities for future break-through discoveries. In this review, we highlight the most important findings that establish cysteine cathepsins as important players in the extracellular space and discuss their roles that reach beyond processing and degradation of extracellular matrix (ECM) components. In addition, we discuss the recent developments in cathepsin research and the new possibilities that are opening in translational medicine.


Assuntos
Catepsinas/metabolismo , Microambiente Celular , Cisteína/metabolismo , Matriz Extracelular/metabolismo , Humanos , Modelos Moleculares , Pesquisa Translacional Biomédica
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