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Targeting Toll-like Receptor (TLR) Pathways in Inflammatory Arthritis: Two Better Than One?

Inflammatory arthritis is a cluster of diseases caused by unregulated activity of the immune system. The lost homeostasis is followed by the immune attack of one’s self, what damages healthy cells and tissues and leads to chronic inflammation of various tissues and organs (e.g., joints, lungs, heart...

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Detalles Bibliográficos
Autor principal: Santos-Sierra, Sandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464963/
https://www.ncbi.nlm.nih.gov/pubmed/34572504
http://dx.doi.org/10.3390/biom11091291
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author Santos-Sierra, Sandra
author_facet Santos-Sierra, Sandra
author_sort Santos-Sierra, Sandra
collection PubMed
description Inflammatory arthritis is a cluster of diseases caused by unregulated activity of the immune system. The lost homeostasis is followed by the immune attack of one’s self, what damages healthy cells and tissues and leads to chronic inflammation of various tissues and organs (e.g., joints, lungs, heart, eyes). Different medications to control the excessive immune response are in use, however, drug resistances, flare-reactions and adverse effects to the current therapies are common in the affected patients. Thus, it is essential to broaden the spectrum of alternative treatments and to develop disease-modifying drugs. In the last 20 years, the involvement of the innate immune receptors TLRs in inflammatory arthritis has been widely investigated and targeting either the receptor itself or the proteins in the downstream signalling cascades has emerged as a promising therapeutic strategy. Yet, concerns about the use of pharmacological agents that inhibit TLR activity and may leave the host unprotected against invading pathogens and toxicity issues amid inhibition of downstream kinases crucial in various cellular functions have arisen. This review summarizes the existing knowledge on the role of TLRs in inflammatory arthritis; in addition, the likely druggable related targets and the developed inhibitors, and discusses the pros and cons of their potential clinical use.
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spelling pubmed-84649632021-09-27 Targeting Toll-like Receptor (TLR) Pathways in Inflammatory Arthritis: Two Better Than One? Santos-Sierra, Sandra Biomolecules Review Inflammatory arthritis is a cluster of diseases caused by unregulated activity of the immune system. The lost homeostasis is followed by the immune attack of one’s self, what damages healthy cells and tissues and leads to chronic inflammation of various tissues and organs (e.g., joints, lungs, heart, eyes). Different medications to control the excessive immune response are in use, however, drug resistances, flare-reactions and adverse effects to the current therapies are common in the affected patients. Thus, it is essential to broaden the spectrum of alternative treatments and to develop disease-modifying drugs. In the last 20 years, the involvement of the innate immune receptors TLRs in inflammatory arthritis has been widely investigated and targeting either the receptor itself or the proteins in the downstream signalling cascades has emerged as a promising therapeutic strategy. Yet, concerns about the use of pharmacological agents that inhibit TLR activity and may leave the host unprotected against invading pathogens and toxicity issues amid inhibition of downstream kinases crucial in various cellular functions have arisen. This review summarizes the existing knowledge on the role of TLRs in inflammatory arthritis; in addition, the likely druggable related targets and the developed inhibitors, and discusses the pros and cons of their potential clinical use. MDPI 2021-08-30 /pmc/articles/PMC8464963/ /pubmed/34572504 http://dx.doi.org/10.3390/biom11091291 Text en © 2021 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Santos-Sierra, Sandra
Targeting Toll-like Receptor (TLR) Pathways in Inflammatory Arthritis: Two Better Than One?
title Targeting Toll-like Receptor (TLR) Pathways in Inflammatory Arthritis: Two Better Than One?
title_full Targeting Toll-like Receptor (TLR) Pathways in Inflammatory Arthritis: Two Better Than One?
title_fullStr Targeting Toll-like Receptor (TLR) Pathways in Inflammatory Arthritis: Two Better Than One?
title_full_unstemmed Targeting Toll-like Receptor (TLR) Pathways in Inflammatory Arthritis: Two Better Than One?
title_short Targeting Toll-like Receptor (TLR) Pathways in Inflammatory Arthritis: Two Better Than One?
title_sort targeting toll-like receptor (tlr) pathways in inflammatory arthritis: two better than one?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464963/
https://www.ncbi.nlm.nih.gov/pubmed/34572504
http://dx.doi.org/10.3390/biom11091291
work_keys_str_mv AT santossierrasandra targetingtolllikereceptortlrpathwaysininflammatoryarthritistwobetterthanone