The Therapeutic Potential of Supersulfides in Oxidative Stress-Related Diseases

Oxidation-reduction (redox) reactions are fundamental to sustaining life, with reactive oxygen and nitrogen species playing pivotal roles in cellular signaling and homeostasis. However, excessive oxidative stress disrupts redox balance, contributing to a wide range of diseases, including inflammator...

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Main Authors: Yuexuan Pan, Tetsuro Matsunaga, Tianli Zhang, Takaaki Akaike
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/2/172
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author Yuexuan Pan
Tetsuro Matsunaga
Tianli Zhang
Takaaki Akaike
author_facet Yuexuan Pan
Tetsuro Matsunaga
Tianli Zhang
Takaaki Akaike
author_sort Yuexuan Pan
collection DOAJ
description Oxidation-reduction (redox) reactions are fundamental to sustaining life, with reactive oxygen and nitrogen species playing pivotal roles in cellular signaling and homeostasis. However, excessive oxidative stress disrupts redox balance, contributing to a wide range of diseases, including inflammatory and pulmonary disorders, neurodegeneration, and cancer. Although numerous antioxidant therapies have been developed and tested for oxidative stress-related diseases, their clinical efficacy remains limited. Here, we introduce the emerging concept of ‘supersulfides’, a class of redox molecule species with unique antioxidant and nucleophilic properties, which have recently been recognized as crucial regulators of cellular redox homeostasis. Unlike traditional antioxidants, supersulfides offer novel mechanisms of action that directly target the underlying processes of oxidative stress. This review summarizes current knowledge on supersulfides, highlighting their roles in oxidative stress and associated diseases, as well as the mechanisms underlying oxidative stress-related pathology. The therapeutic potential of synthetic supersulfides for treating oxidative stress-related diseases is also discussed. A comprehensive understanding of the molecular and cellular basis of redox biology can help to guide the development of innovative redox-based therapeutic strategies aimed at preventing and treating diseases associated with disturbed redox regulation.
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spelling doaj-art-efcb7f80e72d403a8f519818e9722ab82025-08-20T02:44:36ZengMDPI AGBiomolecules2218-273X2025-01-0115217210.3390/biom15020172The Therapeutic Potential of Supersulfides in Oxidative Stress-Related DiseasesYuexuan Pan0Tetsuro Matsunaga1Tianli Zhang2Takaaki Akaike3Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanCenter for Integrated Control, Epidemiology and Molecular Pathophysiology of Infectious Diseases, Akita University, Akita 010-8543, JapanCenter for Integrated Control, Epidemiology and Molecular Pathophysiology of Infectious Diseases, Akita University, Akita 010-8543, JapanDepartment of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanOxidation-reduction (redox) reactions are fundamental to sustaining life, with reactive oxygen and nitrogen species playing pivotal roles in cellular signaling and homeostasis. However, excessive oxidative stress disrupts redox balance, contributing to a wide range of diseases, including inflammatory and pulmonary disorders, neurodegeneration, and cancer. Although numerous antioxidant therapies have been developed and tested for oxidative stress-related diseases, their clinical efficacy remains limited. Here, we introduce the emerging concept of ‘supersulfides’, a class of redox molecule species with unique antioxidant and nucleophilic properties, which have recently been recognized as crucial regulators of cellular redox homeostasis. Unlike traditional antioxidants, supersulfides offer novel mechanisms of action that directly target the underlying processes of oxidative stress. This review summarizes current knowledge on supersulfides, highlighting their roles in oxidative stress and associated diseases, as well as the mechanisms underlying oxidative stress-related pathology. The therapeutic potential of synthetic supersulfides for treating oxidative stress-related diseases is also discussed. A comprehensive understanding of the molecular and cellular basis of redox biology can help to guide the development of innovative redox-based therapeutic strategies aimed at preventing and treating diseases associated with disturbed redox regulation.https://www.mdpi.com/2218-273X/15/2/172supersulfidespersulfidespolysulfidesreactive sulfur speciesoxidative stressreactive oxygen species
spellingShingle Yuexuan Pan
Tetsuro Matsunaga
Tianli Zhang
Takaaki Akaike
The Therapeutic Potential of Supersulfides in Oxidative Stress-Related Diseases
Biomolecules
supersulfides
persulfides
polysulfides
reactive sulfur species
oxidative stress
reactive oxygen species
title The Therapeutic Potential of Supersulfides in Oxidative Stress-Related Diseases
title_full The Therapeutic Potential of Supersulfides in Oxidative Stress-Related Diseases
title_fullStr The Therapeutic Potential of Supersulfides in Oxidative Stress-Related Diseases
title_full_unstemmed The Therapeutic Potential of Supersulfides in Oxidative Stress-Related Diseases
title_short The Therapeutic Potential of Supersulfides in Oxidative Stress-Related Diseases
title_sort therapeutic potential of supersulfides in oxidative stress related diseases
topic supersulfides
persulfides
polysulfides
reactive sulfur species
oxidative stress
reactive oxygen species
url https://www.mdpi.com/2218-273X/15/2/172
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