Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Okayama, Japan.
Nat Rev Nephrol. 2024 Feb;20(2):101-119. doi: 10.1038/s41581-023-00775-0. Epub 2023 Oct 19.
Chronic kidney disease (CKD) is a major public health concern, underscoring a need to identify pathogenic mechanisms and potential therapeutic targets. Reactive oxygen species (ROS) are derivatives of oxygen molecules that are generated during aerobic metabolism and are involved in a variety of cellular functions that are governed by redox conditions. Low levels of ROS are required for diverse processes, including intracellular signal transduction, metabolism, immune and hypoxic responses, and transcriptional regulation. However, excess ROS can be pathological, and contribute to the development and progression of chronic diseases. Despite evidence linking elevated levels of ROS to CKD development and progression, the use of low-molecular-weight antioxidants to remove ROS has not been successful in preventing or slowing disease progression. More recent advances have enabled evaluation of the molecular interactions between specific ROS and their targets in redox signalling pathways. Such studies may pave the way for the development of sophisticated treatments that allow the selective control of specific ROS-mediated signalling pathways.
慢性肾脏病（CKD）是一个主要的公共卫生关注点，这凸显了确定致病机制和潜在治疗靶点的必要性。活性氧（ROS）是有氧代谢过程中产生的氧分子的衍生物，参与多种细胞功能，这些功能受氧化还原条件的控制。低水平的 ROS 对于包括细胞内信号转导、代谢、免疫和缺氧反应以及转录调节在内的各种过程是必需的。然而，过量的 ROS 可能是病理性的，并导致慢性疾病的发展和进展。尽管有证据表明 ROS 水平升高与 CKD 的发生和进展有关，但使用低分子量抗氧化剂去除 ROS 并没有成功地预防或减缓疾病的进展。最近的进展使评估特定 ROS 与氧化还原信号通路中其靶标的分子相互作用成为可能。这些研究可能为开发复杂的治疗方法铺平道路，从而允许选择性控制特定的 ROS 介导的信号通路。
