Circulating biomarkers of ferroptosis: A new frontier in the diagnosis and biological monitoring of cardiovascular and neurodegenerative diseases

Abstract

Ferroptosis is defined as a novel pathway of regulated, iron-dependent cell death. It relies on three main metabolic pathways: iron metabolism, lipid peroxidation, and the GSH/GPX4 antioxidant system. Several studies have shown that this cell death process is implicated in the pathophysiology of numerous chronic diseases, particularly cardiovascular diseases (myocardial infarction, heart failure, cardiomyopathy, ischemia-reperfusion injury) and neurodegenerative disorders (Parkinson's disease, Alzheimer's disease, etc.). Circulating biomarkers of ferroptosis—such as MDA, 4-HNE, isoprostanes, oxidized phospholipids, GPX4, and GSH, as well as markers of iron metabolism—represent promising diagnostic and prognostic tools that could revolutionize the management of patients with these conditions. However, further efforts are required before these parameters can be adopted for routine clinical use. The aim of this work is to summarize current knowledge regarding the main circulating biomarkers of ferroptosis and to examine their potential as diagnostic tools for cardiovascular and neurodegenerative diseases.