Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1 rue Michel Servet, 1211 Geneva, Switzerland.
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1 rue Michel Servet, 1211 Geneva, Switzerland.
Cytokine. 2018 Sep;109:81-93. doi: 10.1016/j.cyto.2018.02.018.
Because of the level of attention it received due to its role as the principal HIV coreceptor, CCR5 has been described as a 'celebrity' chemokine receptor. Here we describe the development of CCR5 inhibitory strategies that have been developed for HIV therapy and which are now additionally being considered for use in HIV prevention and cure. The wealth of CCR5-related tools that have been developed during the intensive investigation of CCR5 as an HIV drug target can now be turned towards the study of CCR5 as a model chemokine receptor. We also summarize what is currently known about the cell biology and pharmacology of CCR5, providing an update on new areas of investigation that have emerged in recent research. Finally, we discuss the potential of CCR5 as a drug target for diseases other than HIV, discussing the evidence linking CCR5 and its natural chemokine ligands with inflammatory diseases, particularly neuroinflammation, and certain cancers. These pathologies may provide new uses for the strategies for CCR5 blockade originally developed to combat HIV/AIDS.
由于其作为主要 HIV 核心受体的作用，CCR5 受到了高度关注，被誉为“明星”趋化因子受体。在这里，我们描述了为 HIV 治疗开发的 CCR5 抑制策略，这些策略现在也被考虑用于 HIV 的预防和治疗。在深入研究 CCR5 作为 HIV 药物靶点的过程中，已经开发了大量与 CCR5 相关的工具，现在可以将这些工具用于研究 CCR5 作为模型趋化因子受体。我们还总结了目前已知的 CCR5 的细胞生物学和药理学知识，提供了关于最近研究中出现的新研究领域的最新信息。最后，我们讨论了 CCR5 作为除 HIV 以外的疾病的药物靶点的潜力，讨论了将 CCR5 及其天然趋化因子配体与炎症性疾病（特别是神经炎症和某些癌症）联系起来的证据。这些病理学可能为最初开发用于对抗 HIV/AIDS 的 CCR5 阻断策略提供新的用途。
