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Journal Article Review Epublish 4 citations

PubMed: 40050273 DOI: 10.1038/s41392-024-02095-6

Redox regulation: mechanisms, biology and therapeutic targets in diseases.

Signal Transduct Target Ther 10(1):72

Authors: Bowen Li, Hui Ming, Siyuan Qin, Edouard C Nice, Jingsi Dong, Zhongyan Du, Canhua Huang

Affiliations

  • Department of Biotherapy, Institute of Oxidative Stress Medicine, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, PR China.
  • Department of Biotherapy, Institute of Oxidative Stress Medicine, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, PR China. Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu, PR China.
  • Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.
  • Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China. Key Laboratory of Blood-stasis-toxin Syndrome of Zhejiang Province, Hangzhou, China.
  • Department of Biotherapy, Institute of Oxidative Stress Medicine, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, PR China. Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu, PR China.

Abstract

Redox signaling acts as a critical mediator in the dynamic interactions between organisms and their external environment, profoundly influencing both the onset and progression of various diseases. Under physiological conditions, oxidative free radicals generated by the mitochondrial oxidative respiratory chain, endoplasmic reticulum, and NADPH oxidases can be effectively neutralized by NRF2-mediated antioxidant responses. These responses elevate the synthesis of superoxide dismutase (SOD), catalase, as well as key molecules like nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH), thereby maintaining cellular redox homeostasis. Disruption of this finely tuned equilibrium is closely linked to the pathogenesis of a wide range of diseases. Recent advances have broadened our understanding of the molecular mechanisms underpinning this dysregulation, highlighting the pivotal roles of genomic instability, epigenetic modifications, protein degradation, and metabolic reprogramming. These findings provide a foundation for exploring redox regulation as a mechanistic basis for improving therapeutic strategies. While antioxidant-based therapies have shown early promise in conditions where oxidative stress plays a primary pathological role, their efficacy in diseases characterized by complex, multifactorial etiologies remains controversial. A deeper, context-specific understanding of redox signaling, particularly the roles of redox-sensitive proteins, is critical for designing targeted therapies aimed at re-establishing redox balance. Emerging small molecule inhibitors that target specific cysteine residues in redox-sensitive proteins have demonstrated promising preclinical outcomes, setting the stage for forthcoming clinical trials. In this review, we summarize our current understanding of the intricate relationship between oxidative stress and disease pathogenesis and also discuss how these insights can be leveraged to optimize therapeutic strategies in clinical practice.

MeSH

Stress, Physiological, Nadp, Oxidative Stress, Antioxidants, Signal Transduction, Therapeutics

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