Drug Addiction Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23507, USA.
Center for Integrative Neuroscience and Inflammatory Diseases, Eastern Virginia Medical School, Norfolk, VA 23507, USA.
Biomolecules. 2023 May 31;13(6):922. doi: 10.3390/biom13060922.
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.
在过去的十年中，物质使用障碍（SUDs）已被越来越多地认为是与神经炎症相关的脑部疾病。各种滥用药物（可卡因、冰毒、酒精、类阿片药物、大麻等）可以调节小胶质细胞的激活状态和神经炎症水平，而这些都参与了 SUDs 的发病机制。几种神经免疫信号通路，包括 TLR/NF-кB、活性氧、线粒体功能障碍以及自噬缺陷等，都与促进 SUDs 有关。最近，炎症小体介导的信号被认为在滥用药物诱导的小胶质细胞激活中起关键作用。在炎症小体家族中，NOD、LRR 和 pyrin 结构域包含蛋白 3（NLRP3）由于其在小胶质细胞中的丰富表达，成为主要的研究靶标。NLRP3 具有整合多种内外输入的能力，并在各种病理条件下协调确定小胶质细胞激活的强度。在这里，我们总结了滥用药物对 NLRP3 炎症小体的影响，以及其他可能的影响。对这一课题的研究仍处于起步阶段；然而，现有的研究结果表明，NLRP3 炎症小体可能是各种类型的滥用药物刺激的共同下游效应子，并通过增强胶质细胞-神经元通讯，在决定滥用药物介导的生物学效应中发挥关键作用。NLRP3 炎症小体可能成为改善 SUDs 发展的新靶点。
