GPX4 ferroptosis, rheumatoid arthritis, lipid peroxidation, biomarkers, iron metabolism, Therapeutics
DOI:
https://doi.org/10.64261/4jcc2h05Keywords:
GPX4 ferroptosis, rheumatoid arthritis, lipid peroxidation, biomarkers, iron metabolism, TherapeuticsAbstract
Rheumatoid arthritis (RA) refers to a chronic autoimmune condition that is typified by chronic inflammation of the synovium, progressive destruction of the joints, and systemic comorbidities. Ferroptosis - an iron-dependent regulated cell death mediated by lipid peroxidation has been studied as an increasing body of evidence in RA pathophysiology over the past few years. Central to the ferroptosis process is the Glutathione peroxidase 4 (GPX4), which helps to balance lipid redox through the depletion of lipid hydroperoxides.GPX4 and related ferroptotic damage dysregulation could also be involved in RA-associated synovial cell death, cartilage degeneration, and inflammatory exaggeration. The synthesis of mechanistic understanding of ferroptosis, a summary of candidate biomarkers (including GPX4 expression and activity, lipid peroxidation products, iron handling proteins, and system Xc- components), and an analysis of therapeutic interventions aimed at ferroptosis (GPX4 modulators, iron chelators, lipid-peroxidation inhibitors, and combined therapeutic strategies) are summarized in this review. We address the problem of translational challenges, such as standardization of biomarkers, tissue specificity, safety of long-term anti-ferroptotic treatment, and suggest a road map towards clinical application of this therapeutic approach, including biomarker-assisted patient stratification, and combination therapies with existing disease-modifying antirheumatic drugs (DMARDs). This review aims to make ferroptosis and GPX4-focused biomarkers an attractive innovation in the field of RA diagnostics, prognosis, and treatment.
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