Liao Jiangfeng, Zhang Yusi, Yang Jianwei, Chen Longfei, Zhang Jing, Chen Xiaochun
Department of Neurology, Institute of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350001, China.
Department of Neurology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China.
Antioxidants (Basel). 2025 Mar 23;14(4):379. doi: 10.3390/antiox14040379.
As a moonlighting protein with multiple enzymatic activities, peroxiredoxin 6 (PRDX6) maintains redox homeostasis, regulates phospholipid metabolism, and mediates intra- and inter-cellular signaling transduction. Its expression and activity can be regulated by diverse stressors. However, the roles and relevant mechanisms of these regulators in various conditions have yet to be comprehensively reviewed. In this study, these stressors were systematically reviewed both in vivo and in vitro and classified into chemical, physical, and biological categories. We found that the regulatory effects of these stressors on PRDX6 expression were primarily mediated via key transcriptional factors (e.g., NRF2, HIF-1α, SP1, and NF-κB), micro-RNAs, and receptor- or kinase-dependent signaling pathways. Additionally, certain stressors, including reactive oxygen species, pH fluctuations, and post-translational modifications, induced the structure-based functional switches in the PRDX6 enzyme. We further reviewed the altered expression of PRDX6 under various disease conditions, with a particular focus on neuropsychiatric disorders and cancers, and proposed the concept of PRDX6-related disorders (PRD), which refers to a spectrum of diseases mediated by or associated with dysregulated PRDX6 expression. Finally, we found that an exogenous supplementation of PRDX6 protein provided preventive and therapeutic potentials for oxidative stress-related injuries in both in vivo and in vitro models. Taken together, this review underscores the critical role of PRDX6 as a cellular orchestrator in response to various stressors, highlighting its clinical potential for disease monitoring and the development of therapeutic strategies.
作为一种具有多种酶活性的兼职蛋白，过氧化物还原酶6（PRDX6）维持氧化还原稳态，调节磷脂代谢，并介导细胞内和细胞间信号转导。其表达和活性可受多种应激源调控。然而，这些调节因子在不同条件下的作用及相关机制尚未得到全面综述。在本研究中，我们对这些应激源进行了体内和体外的系统综述，并将其分为化学、物理和生物类别。我们发现，这些应激源对PRDX6表达的调节作用主要通过关键转录因子（如NRF2、HIF-1α、SP1和NF-κB）、微小RNA以及受体或激酶依赖性信号通路介导。此外，某些应激源，包括活性氧、pH波动和翻译后修饰，可诱导PRDX6酶基于结构的功能转换。我们进一步综述了PRDX6在各种疾病条件下的表达变化，尤其关注神经精神疾病和癌症，并提出了PRDX6相关疾病（PRD）的概念，它指的是由PRDX6表达失调介导或与之相关的一系列疾病。最后，我们发现外源性补充PRDX6蛋白在体内和体外模型中均为氧化应激相关损伤提供了预防和治疗潜力。综上所述，本综述强调了PRDX6作为细胞协调因子在应对各种应激源中的关键作用，突出了其在疾病监测和治疗策略开发方面的临床潜力。
