1 Experimental and Molecular Pediatric Cardiology, German Heart Center Munich , TU Munich, Munich, Germany .
2 DZHK (German Centre for Cardiovascular Research) , Partner Site Munich, Munich Heart Alliance, Munich, Germany .
Antioxid Redox Signal. 2019 Jan 1;30(1):74-94. doi: 10.1089/ars.2018.7525. Epub 2018 Apr 25.
G protein-coupled receptors (GPCR) are the largest group of cell surface receptors, which link cells to their environment. Reactive oxygen species (ROS) can act as important cellular signaling molecules. The family of NADPH oxidases generates ROS in response to activated cell surface receptors. Recent Advances: Various signaling pathways linking GPCRs and activation of NADPH oxidases have been characterized.
Still, a more detailed analysis of G proteins involved in the GPCR-mediated activation of NADPH oxidases is needed. In addition, a more precise discrimination of NADPH oxidase activation due to either upregulation of subunit expression or post-translational subunit modifications is needed. Also, the role of noncanonical modulators of NADPH oxidase activation in the response to GPCRs awaits further analyses.
As GPCRs are one of the most popular classes of investigational drug targets, further detailing of G protein-coupled mechanisms in the activation mechanism of NADPH oxidases as well as better understanding of the link between newly identified NADPH oxidase interaction partners and GPCR signaling will provide new opportunities for improved efficiency and decreased off target effects of therapies targeting GPCRs.
G 蛋白偶联受体（GPCR）是细胞表面受体中最大的一组，它们将细胞与其环境联系起来。活性氧（ROS）可以作为重要的细胞信号分子。NADPH 氧化酶家族在细胞表面受体激活时产生 ROS。
已经描述了将 GPCR 与 NADPH 氧化酶激活相关联的各种信号通路。
仍需要更详细地分析参与 GPCR 介导的 NADPH 氧化酶激活的 G 蛋白。此外，需要更精确地区分 NADPH 氧化酶激活是由于亚基表达的上调还是翻译后亚基修饰引起的。另外，非典型 NADPH 氧化酶激活调节剂在 GPCR 反应中的作用也需要进一步分析。
由于 GPCR 是最受欢迎的一类研究性药物靶标之一，因此详细阐述 NADPH 氧化酶激活机制中的 G 蛋白偶联机制，以及更好地理解新鉴定的 NADPH 氧化酶相互作用伙伴与 GPCR 信号之间的联系，将为提高靶向 GPCR 治疗的效率和降低脱靶效应提供新的机会。
