在过去的十年里,物质使用障碍(SUDs)越来越被认为是神经炎症相关的脑部疾病.各种类型的滥用药物(可卡因,甲基苯丙胺,酒精,阿片类药物,大麻,等。)可以调节与SUD发病机理有关的小胶质细胞的激活状态和神经炎症水平。几种神经免疫信号通路,包括TLR/NF-KB,活性氧,线粒体功能障碍,以及自噬缺陷,等。,参与了SUD的推广。最近,炎症小体介导的信号传导在滥用药物诱导的小胶质细胞激活中起关键作用。在炎性体家族中,NOD-,LRR-,含pyrin结构域的蛋白3(NLRP3)由于其在小胶质细胞中的丰富表达而成为主要研究目标。NLRP3具有整合多个外部和内部输入并在各种病理条件下协调确定小胶质细胞激活强度的能力。这里,我们总结了滥用药物对NLRP3炎性体的影响,以及其他人,如果有的话。关于这一主题的研究仍处于起步阶段;然而,现有的研究结果表明,NLRP3炎性体可能是受各种类型滥用药物刺激的常见下游效应物,并通过增强神经胶质-神经元通讯在确定滥用药物介导的生物学效应方面发挥关键作用.NLRP3炎性体可能作为改善SUDs发展的新靶标。
During the last decade, substance use disorders (SUDs) have been increasingly recognized as neuroinflammation-related brain diseases. Various types of abused drugs (cocaine, methamphetamine, alcohol, opiate-like drugs, marijuana, etc.) can modulate the activation status of microglia and neuroinflammation levels which are involved in the pathogenesis of SUDs. Several neuroimmune signaling pathways, including TLR/NF-кB, reactive oxygen species, mitochondria dysfunction, as well as autophagy defection, etc., have been implicated in promoting SUDs. Recently, inflammasome-mediated signaling has been identified as playing critical roles in the microglia activation induced by abused drugs. Among the family of inflammasomes, NOD-, LRR-, and pyrin-domain-containing protein 3 (NLRP3) serves the primary research target due to its abundant expression in microglia. NLRP3 has the capability of integrating multiple external and internal inputs and coordinately determining the intensity of microglia activation under various pathological conditions. Here, we summarize the effects of abused drugs on NLRP3 inflammasomes, as well as others, if any. The research on this topic is still at an infant stage; however, the readily available findings suggest that NLRP3 inflammasome could be a common downstream effector stimulated by various types of abused drugs and play critical roles in determining abused-drug-mediated biological effects through enhancing glia-neuron communications. NLRP3 inflammasome might serve as a novel target for ameliorating the development of SUDs.