Peroxiredoxins in disease biology: molecular mechanisms and therapeutic opportunities

Peroxiredoxins (PRDXs) are thiol-specific antioxidant enzymes that maintain cellular redox balance and regulate signaling pathways. They participate in the development of cancer, neurodegenerative disorders, cardiovascular diseases, inflammatory conditions, and infectious diseases. In cancer, PRDXs are frequently overexpressed and promote tumor progression, metastasis, and treatment resistance through interactions with oncogenic pathways. In neurodegenerative and cardiovascular diseases, by contrast, they support cell survival by limiting oxidative damage. Therapeutic strategies directed at PRDXs include small-molecule inhibitors, activators, and gene therapy. PRDX inhibitors sensitize tumor cells to oxidative damage, whereas PRDX activators confer neuroprotection; the principal obstacles are achieving isoform specificity and limiting off-target effects. Here we review the structure and biology of the PRDX family, its isoform- and context-dependent functions across these disease settings, and the evidence supporting PRDXs as therapeutic targets and prognostic biomarkers.