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Toll-like receptor 4: A promising crossroads in the diagnosis and treatment of several pathologies.
Eur J Pharmacol. 2020 May 05; 874:172975.EJ

Abstract

Toll-like receptor 4 (TLR4) is expressed in a wide variety of cells and is the central component of the mammalian innate immune system. Since its discovery in 1997, TLR4 has been assigned an ever-increasing number of functions that extend from pathogen recognition to tissue damage identification and promotion of the intrinsic "damage repair response" in pain, intestinal, respiratory and vascular disorders. Precisely, the finding of conserved sequence homology among species along with the molecular and functional characterisation of the TLR4 gene enabled researchers to envisage a common operating system in the activation of innate immunity and the initiation of plastic changes at the onset of chronic pain. Malfunctioning in other conditions was conceived in parallel. In this respect, "pivot" proteins and pathway redundancy are not just evolutionary leftovers but essential for normal functioning or cell survival. Indeed, at present, TLR4 single nucleotide polymorphisms (SNP) and their association with certain dysfunctions and diseases are being confirmed in different pools of patients. However, despite its ability to trigger pathogen infection or alternatively tissue injury communications to immune system, TLR4 targeting might not be considered a panacea. This review article represents a compilation of what we know about TLR4 from clinics and basic research on the 20th anniversary of its discovery. Understanding how to fine-tune the interaction between TLR4 and its specific ligands may lead in the next decades to the development of promising new treatments, reducing polypharmacy and probably having an impact on drug use in numerous pathologies.

Authors+Show Affiliations

Area of Pharmacology, Nutrition and Bromatology, Department of Basic Health Sciences, Universidad Rey Juan Carlos, Avda, Atenas S/n, 28922, Alcorcón, Spain.Area of Pharmacology, Nutrition and Bromatology, Department of Basic Health Sciences, Universidad Rey Juan Carlos, Avda, Atenas S/n, 28922, Alcorcón, Spain.Area of Pharmacology, Nutrition and Bromatology, Department of Basic Health Sciences, Universidad Rey Juan Carlos, Avda, Atenas S/n, 28922, Alcorcón, Spain.Area of Pharmacology, Nutrition and Bromatology, Department of Basic Health Sciences, Universidad Rey Juan Carlos, Avda, Atenas S/n, 28922, Alcorcón, Spain. Electronic address: david.pascual@urjc.es.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32017939

Citation

Garcia, Miguel M., et al. "Toll-like Receptor 4: a Promising Crossroads in the Diagnosis and Treatment of Several Pathologies." European Journal of Pharmacology, vol. 874, 2020, p. 172975.
Garcia MM, Goicoechea C, Molina-Álvarez M, et al. Toll-like receptor 4: A promising crossroads in the diagnosis and treatment of several pathologies. Eur J Pharmacol. 2020;874:172975.
Garcia, M. M., Goicoechea, C., Molina-Álvarez, M., & Pascual, D. (2020). Toll-like receptor 4: A promising crossroads in the diagnosis and treatment of several pathologies. European Journal of Pharmacology, 874, 172975. https://doi.org/10.1016/j.ejphar.2020.172975
Garcia MM, et al. Toll-like Receptor 4: a Promising Crossroads in the Diagnosis and Treatment of Several Pathologies. Eur J Pharmacol. 2020 May 5;874:172975. PubMed PMID: 32017939.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Toll-like receptor 4: A promising crossroads in the diagnosis and treatment of several pathologies. AU - Garcia,Miguel M, AU - Goicoechea,Carlos, AU - Molina-Álvarez,Miguel, AU - Pascual,David, Y1 - 2020/02/01/ PY - 2019/05/31/received PY - 2019/12/20/revised PY - 2020/01/29/accepted PY - 2020/2/6/pubmed PY - 2020/2/6/medline PY - 2020/2/5/entrez KW - DAMP KW - Glia KW - PAMP KW - Pain KW - Toll-like receptor 4 SP - 172975 EP - 172975 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 874 N2 - Toll-like receptor 4 (TLR4) is expressed in a wide variety of cells and is the central component of the mammalian innate immune system. Since its discovery in 1997, TLR4 has been assigned an ever-increasing number of functions that extend from pathogen recognition to tissue damage identification and promotion of the intrinsic "damage repair response" in pain, intestinal, respiratory and vascular disorders. Precisely, the finding of conserved sequence homology among species along with the molecular and functional characterisation of the TLR4 gene enabled researchers to envisage a common operating system in the activation of innate immunity and the initiation of plastic changes at the onset of chronic pain. Malfunctioning in other conditions was conceived in parallel. In this respect, "pivot" proteins and pathway redundancy are not just evolutionary leftovers but essential for normal functioning or cell survival. Indeed, at present, TLR4 single nucleotide polymorphisms (SNP) and their association with certain dysfunctions and diseases are being confirmed in different pools of patients. However, despite its ability to trigger pathogen infection or alternatively tissue injury communications to immune system, TLR4 targeting might not be considered a panacea. This review article represents a compilation of what we know about TLR4 from clinics and basic research on the 20th anniversary of its discovery. Understanding how to fine-tune the interaction between TLR4 and its specific ligands may lead in the next decades to the development of promising new treatments, reducing polypharmacy and probably having an impact on drug use in numerous pathologies. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/32017939/Toll-like_receptor_4:_A_promising_crossroads_in_the_diagnosis_and_treatment_of_several_pathologies L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(20)30067-4 DB - PRIME DP - Unbound Medicine ER -
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