Fitzpatrick John-Mark K, Downer Eric J
Department of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, University of Dublin, Trinity College, Dublin 2, Ireland.
Department of Physiology, School of Medicine, Trinity Biomedical Sciences Institute, University of Dublin, Trinity College, Dublin 2, Ireland.
Neuropharmacology. 2017 Feb;113(Pt B):618-626. doi: 10.1016/j.neuropharm.2016.04.009. Epub 2016 Apr 11.
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'.
Toll样受体（TLRs）是病原体相关分子的传感器，可触发特定的先天性免疫细胞内信号反应，从而启动先天性免疫反应。实验性自身免疫性脑脊髓炎（EAE）模型的数据表明，TLR信号传导机制在小鼠EAE的发展中起着关键作用。更复杂的是，来自人体研究的数据表明，TLR信号传导与多发性硬化症（MS）发病机制之间存在复杂的相互作用。基于大麻的疗法正在临床开发中，用于治疗包括MS在内的多种医疗状况。特别是Sativex，一种植物源性大麻素的组合，是一种口腔黏膜喷雾剂，对MS患者有效，尤其是那些患有神经性疼痛和痉挛的患者。尽管如此，Sativex在MS患者中的确切细胞和分子作用机制仍不清楚。本综述将强调有证据表明，TLR和大麻素系统在中枢和外周均存在新的相互作用，这与MS的发病机制相关。本文是名为“中枢神经系统中脂质传感G蛋白偶联受体”的特刊的一部分。
