General thiol-containing proteins and redox-sensitive signaling molecules

General thiol-containing proteins and redox-sensitive signaling molecules, collectively known as the redoxome, represent a vast network of proteins that utilize the chemical reactivity of cysteine sulfhydryl (-SH) groups to sense and respond to cellular oxidative stress (Go, Y. M., & Jones, D. P., 2013, Free Radical Biology and Medicine). These molecules act as biological switches where the reversible oxidation of thiol groups regulates enzymatic activity, protein-protein interactions, and gene expression (Janssen-Heininger, Y. M., et al., 2008, Free Radical Biology and Medicine). Key components include the thioredoxin and glutaredoxin systems, as well as transcription factors like Nrf2 and NF-κB, which coordinate the cellular defense against reactive oxygen species (Manda, G., et al., 2015, Molecules). In pathological states such as cancer, neurodegeneration, and chronic inflammation, the redox balance is often hijacked or severely impaired, leading to disease progression (Rushworth, S. A., & Megson, I. L., 2014, Pharmacology & Therapeutics). Therapeutic interventions often target these molecules using electrophilic drugs that covalently modify specific reactive thiols or antioxidants that replenish the cellular reducing capacity. However, the ubiquity of thiol groups across the proteome poses a significant challenge for drug developers seeking to achieve high specificity and minimize off-target toxicity.

Other names

RedoxomeThiol-redox proteomeCysteine-rich signaling proteinsSulfhydryl-containing proteinsRedox-sensitive proteome

Modification of cysteine thiol groups through S-nitrosylation, S-glutathionylation, or disulfide bond formation to modulate protein activity, or the use of electrophilic molecules to activate the Nrf2-mediated antioxidant response element (ARE) pathway.