Opsona Therapeutics Ltd., Institute of Molecular Medicine, Trinity Centre for Health Sciences, St. James' Hospital, Dublin 8, Ireland.
Trends Pharmacol Sci. 2011 Jul;32(7):435-42. doi: 10.1016/j.tips.2011.03.008. Epub 2011 Apr 27.
Since the identification of the first Toll-like receptor (TLR) in humans in 1997, understanding of the molecular basis for innate immunity has increased significantly. The TLR family and downstream signalling pathways have been extensively characterised, There is now significant evidence suggesting a role for TLRs in human inflammatory and immune diseases such as rheumatoid arthritis, diabetes, allergy/asthma and atherosclerosis. Various approaches have been taken to identify novel therapeutic agents targeting TLRs including biologics, small molecules and nucleic acid-based drugs. Several are now being evaluated in the clinic and showing promise against various diseases. This review paper outlines the recent advances in the understanding of TLR biology and highlights novel TLR agonists and antagonists in development for the treatment of immune diseases.
自 1997 年人类首次鉴定出 Toll 样受体 (TLR) 以来,对先天免疫的分子基础的理解有了显著的提高。TLR 家族及其下游信号通路已得到广泛的研究。目前有大量证据表明 TLR 在人类炎症性和免疫性疾病(如类风湿关节炎、糖尿病、过敏/哮喘和动脉粥样硬化)中发挥作用。人们已经采取了各种方法来识别针对 TLR 的新型治疗剂,包括生物制剂、小分子和核酸药物。其中一些目前正在临床评估中,并显示出对各种疾病的治疗潜力。本文概述了 TLR 生物学理解的最新进展,并重点介绍了正在开发用于治疗免疫性疾病的新型 TLR 激动剂和拮抗剂。