Division of Rheumatology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Arch Biochem Biophys. 2019 Jul 30;670:82-93. doi: 10.1016/j.abb.2019.01.031. Epub 2019 Jan 30.
The NLRP3 inflammasome is implicated in the processing of the pro-inflammatory cytokine interleukin 1β. Inflammatory disorders associated with the activation of the NLRP3 inflammasome - IL-1 axis are termed autoinflammatory diseases. Gout is an autoinflammatory disease, which is triggered by the deposition of monosodium urate crystals of precipitated uric acid. It is characterized by recurrent attacks of inflammation due to the activation of phagocytic cells that try to clear the crystals. NLRP3 inflammasome-mediated IL-1β production plays a key role in the manifestation of the disease. Currently, the best approach to treat gout is to reduce uric acid concentration by targeting xanthine oxidase or uric acid transporters, or to use non-steroidal anti-inflammatory drugs. Nevertheless, most of these treatments are not effective enough and may results in side effects. During the past decades, our knowledge has greatly improved about the molecular mechanisms of NLRP3 activation. This knowledge enables and urges scientists to discover or design drugs that target pathways of NLRP3 inflammasome activation, or more preferentially, NLRP3 inflammasome itself. In this review, we discuss the already available drugs and products, that target the diverse pathways of the NLRP3 - IL-1β axis, and the future therapeutic perspectives.
NLRP3 炎性小体与前炎性细胞因子白细胞介素 1β的加工有关。与 NLRP3 炎性小体-IL-1 轴激活相关的炎症性疾病被称为自身炎症性疾病。痛风是一种自身炎症性疾病，由沉淀尿酸的单钠尿酸盐晶体沉积引发。其特征是由于吞噬细胞试图清除晶体而被激活，导致炎症反复发作。NLRP3 炎性小体介导的 IL-1β 产生在疾病的表现中起着关键作用。目前，治疗痛风的最佳方法是通过靶向黄嘌呤氧化酶或尿酸转运体来降低尿酸浓度，或使用非甾体抗炎药。然而，这些治疗方法大多不够有效，可能会产生副作用。在过去的几十年中，我们对 NLRP3 激活的分子机制的认识有了很大的提高。这一知识使科学家们能够发现或设计靶向 NLRP3 炎性小体激活途径的药物，或者更倾向于靶向 NLRP3 炎性小体本身。在这篇综述中，我们讨论了已经可用的药物和产品，这些药物和产品靶向 NLRP3-IL-1β 轴的多种途径，以及未来的治疗前景。
