Toll-like receptor signalling as a cannabinoid target.

Autor: Cui Sun M; Discipline of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland., Otálora-Alcaraz A; Discipline of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland., Prenderville JA; Discipline of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; Transpharmation Ireland Limited, Institute of Neuroscience, Trinity College, Dublin 2, Ireland., Downer EJ; Discipline of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland. Electronic address: edowner@tcd.ie.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2024 Apr; Vol. 222, pp. 116082. Date of Electronic Publication: 2024 Mar 02.
DOI: 10.1016/j.bcp.2024.116082
Abstrakt: Toll-like receptors (TLRs) have become a focus in biomedicine and biomedical research given the roles of this unique family of innate immune proteins in immune activation, infection, and autoimmunity. It is evident that TLR dysregulation, and subsequent alterations in TLR-mediated inflammatory signalling, can contribute to disease pathogenesis, and TLR targeted therapies are in development. This review highlights evidence that cannabinoids are key regulators of TLR signalling. Cannabinoids include component of the plant Cannabis sativa L. (C. sativa), synthetic and endogenous ligands, and overall represent a class of compounds whose therapeutic potential and mechanism of action continues to be elucidated. Cannabinoid-based medicines are in the clinic, and are furthermore under intense investigation for broad clinical development to manage symptoms of a range of disorders. In this review, we present an overview of research evidence that signalling linked to a range of TLRs is targeted by cannabinoids, and such cannabinoid mediated effects represent therapeutic avenues for further investigation. First, we provide an overview of TLRs, adaptors and key signalling events, alongside a summary of evidence that TLRs are linked to disease pathologies. Next, we discuss the cannabinoids system and the development of cannabinoid-based therapeutics. Finally, for the bulk of this review, we systematically outline the evidence that cannabinoids (plant-derived cannabinoids, synthetic cannabinoids, and endogenous cannabinoid ligands) can cross-talk with innate immune signalling governed by TLRs, focusing specifically on each member of the TLR family. Cannabinoids should be considered as key regulators of signalling controlled by TLRs, and such regulation should be a major focus in terms of the anti-inflammatory propensity of the cannabinoid system.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.A.P. is an employee of Transpharmation Ireland. All other authors declare no competing financial interests.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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