Drug Discovery Today ( IF 7.4 ) Pub Date : 2018-01-09 , DOI: 10.1016/j.drudis.2018.01.015 Lingfeng Chen , Weitao Fu , Lulu Zheng , Yi Wang , Guang Liang
Myeloid differentiation protein 2 (MD2), together with Toll-like receptor 4 (TLR4), binds lipopolysaccharide (LPS) with high affinity, inducing the formation of the activated homodimer LPS-MD2-TLR4. MD2 directly recognizes the Lipid A domain of LPS, leading to the activation of downstream signaling of cytokine and chemokine production, and initiation of inflammatory and immune responses. However, excessive activation and potent host responses generate severe inflammatory syndromes such as acute sepsis and septic shock. MD2 is increasingly being considered as an attractive pharmacological target for the development of potent anti-inflammatory agents. In this Keynote review, we provide a comprehensive overview of the recent advances in the structure and biology of MD2, and present MD2 modulators as promising agents for anti-inflammatory intervention.
中文翻译:
炎性疾病的髓样分化2(MD2)调节剂发现的最新进展
髓样分化蛋白2(MD2)与Toll样受体4(TLR4)一起以高亲和力结合脂多糖(LPS),诱导形成活化的同型二聚体LPS-MD2-TLR4。MD2直接识别LPS的脂质A结构域,导致下游激活细胞因子和趋化因子的信号传导,并引发炎症和免疫反应。但是,过度激活和强效宿主反应会产生严重的炎症综合症,例如急性败血症和败血性休克。MD2被越来越多地视为开发有效的抗炎药的有吸引力的药理学靶标。在本主题演讲中,我们提供了MD2的结构和生物学最新进展的全面概述,并提出了MD2调节剂作为抗炎干预的有希望的药物。