Oxidative stress and the role of redox signalling in chronic kidney disease

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 cell...

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Veröffentlicht in:Nature reviews. Nephrology 2024-02, Vol.20 (2), p.101-119
Hauptverfasser: Kishi, Seiji, Nagasu, Hajime, Kidokoro, Kengo, Kashihara, Naoki
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Sprache:eng
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Zusammenfassung: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. Although potentially harmful in excess, reactive oxygen species (ROS) also act as signalling molecules and contribute to cell survival. This Review describes the relevance of ROS to physiological processes and disease pathogenesis with a focus on the kidney. The authors also outline the current status of clinical trials that aim to target ROS signalling in humans. Key points Oxidative stress occurs when the generation of oxidants exceeds the metabolizing or degradative capacity of antioxidants. Reactive oxygen species (ROS) are radical or molecular species that contain oxygen and are produced by cellular organelles; they can cause damage to cells and tissues when present in excessive amounts. Although potentially harmful in excess, ROS also contribute to cell survival and can act as signalling molecules at appropriate intracellular concentrations. Within the kidney, ROS are produced by a variety of organelles and enzyme systems, and contribute to a range of physiological and pathological processes. The involvement of ROS in pathological processes suggests that therapeutic targeting of ROS may be beneficial; a number of therapeutic approaches are under investigation, including targeting of Nrf2.
ISSN:1759-5061
1759-507X
DOI:10.1038/s41581-023-00775-0