Peroxiredoxin 6 (PRDX6) (PRDX6)

Peroxiredoxin 6 (PRDX6) is a unique, multifunctional enzyme belonging to the peroxiredoxin family, distinguished by its 1-Cys catalytic mechanism and its ability to exhibit both glutathione peroxidase and acidic calcium-independent phospholipase A2 (aiPLA2) activities (Fisher, 2018, J Lipid Res). While its peroxidase function is primarily antioxidant, protecting cells from oxidative stress by reducing hydroperoxides, its aiPLA2 activity plays a critical role in phospholipid turnover, lung surfactant homeostasis, and the activation of NADPH oxidase 2 (NOX2) (Arevalo & Vázquez-Medina, 2018, Antioxidants). In pathological contexts, the aiPLA2 activity of PRDX6 is often associated with pro-inflammatory and pro-oxidant effects, contributing to acute lung injury (ALI), ventilator-induced lung injury (VILI), and the progression of various cancers through the promotion of cell invasion and metastasis (Ho et al., 2010, Mol Cancer Ther). Consequently, PRDX6 has emerged as a significant therapeutic target, with inhibitors like the small molecule MJ33 and the peptide PIP-2 being developed to selectively block its phospholipase activity (Fisher et al., 2021, Biomolecules). Targeting this specific enzymatic function offers a strategy to mitigate inflammation and oxidative damage in respiratory and oncological diseases while potentially preserving the protein's protective antioxidant roles (Xue et al., 2024, Frontiers in Cell and Developmental Biology).

Other names

Acidic calcium-independent phospholipase A2aiPLA21-Cys peroxiredoxin1-Cys PrxNon-selenium glutathione peroxidaseNSGPxAntioxidant protein 2AOP2p29

Inhibition of the acidic calcium-independent phospholipase A2 (aiPLA2) activity of Peroxiredoxin 6, which prevents the activation of NADPH oxidase 2 (NOX2) and reduces the release of arachidonic acid, thereby mitigating inflammation and cancer cell metastasis.