title: Toll-like receptor signalling as a cannabinoid target in Multiple Sclerosis.
abstract: Toll-like receptors (TLRs) are the sensors of pathogen-associated molecules that trigger tailored innate immune intracellular signalling responses to initiate innate immune reactions. Data from the experimental autoimmune encephalomyelitis (EAE) model indicates that TLR signalling machinery is a pivotal player in the development of murine EAE. To compound this, data from human studies indicate that complex interplay exists between TLR signalling and Multiple Sclerosis (MS) pathogenesis. Cannabis-based therapies are in clinical development for the management of a variety of medical conditions, including MS. In particular Sativex®, a combination of plant-derived cannabinoids, is an oromucosal spray with efficacy in MS patients, particularly those with neuropathic pain and spasticity. Despite this, the precise cellular and molecular mechanisms of action of Sativex®in MS patients remains unclear. This review will highlight evidence that novel interplay exists between the TLR and cannabinoid systems, both centrally and peripherally, with relevance to the pathogenesis of MS. This article is part of the Special Issue entitled 'Lipid Sensing G Protein-Coupled Receptors in the CNS'.
authors.affiliation: Department of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, University of Dublin, Trinity College, Dublin 2, Ireland.
authors.forename: John-Mark K
authors.initials: JK
authors.lastname: Fitzpatrick
authors.affiliation: Department of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, University of Dublin, Trinity College, Dublin 2, Ireland. Electronic address: edowner@tcd.ie.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Downer
mesh_terms: D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use*; D002186:Cannabinoids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D051193:Toll-Like Receptors
keywords: Cannabinoids; Cell signalling; Innate immunity; Multiple sclerosis; Therapeutics; Toll-like receptor