Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Curr Opin Nephrol Hypertens. 2020 Jan;29(1):128-135. doi: 10.1097/MNH.0000000000000556.
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor which regulates a wider range of downstream pathways than previously thought. This review focuses on the novel findings about the internal regulatory mechanisms of Nrf2, the expanding understanding of its role in maintaining cellular homeostasis and the attempts to broaden the clinical application of its activators.
Nrf2 is in charge of the maintenance of cellular homeostasis under stress and there exist the internal regulatory mechanisms for Nrf2 which have recently been elucidated. New downstream pathways of Nrf2 have been discovered, including the defense against ferroptosis, the latest concept of cell death. Several Nrf2 activators are at various stages of clinical development and are being tested in clinical trials for chronic kidney disease (CKD) including diabetic kidney disease, Alport syndrome, autosomal dominant polycystic kidney disease and focal segmental glomerulosclerosis.
Nrf2 has been gathering attention as an emerging treatment target of chronic diseases which have oxidative stress and inflammation as their pathogenesis including CKD. Basic and clinical studies are under way to establish its role as a target for treatment of those diseases.
核因子红细胞 2 相关因子 2(Nrf2)是一种转录因子,其调控的下游途径比之前认为的更为广泛。本篇综述聚焦于 Nrf2 的内部调控机制的新发现、其在维持细胞内稳态中的作用的不断扩展的理解,以及拓宽其激活剂的临床应用的尝试。
Nrf2 负责在压力下维持细胞内稳态,目前已经阐明了 Nrf2 的内部调控机制。Nrf2 的新下游途径已经被发现,包括对抗铁死亡的防御作用,这是细胞死亡的最新概念。几种 Nrf2 激活剂处于不同的临床开发阶段,正在临床试验中测试用于慢性肾脏病(CKD),包括糖尿病肾病、Alport 综合征、常染色体显性多囊肾病和局灶节段性肾小球硬化症。
Nrf2 作为氧化应激和炎症为发病机制的慢性疾病(包括 CKD)的新兴治疗靶点引起了关注。正在进行基础和临床研究以确定其作为这些疾病治疗靶点的作用。