Ferroptosis pathway (Lipid peroxidation pathway)

Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death that is triggered by the excessive peroxidation of lipids, particularly polyunsaturated fatty acids (PUFAs) in cellular membranes[1][4][6][7]. This process involves three key steps: initiation (hydrogen abstraction from PUFA lipids by reactive oxygen species or iron-catalyzed Fenton reactions); propagation (generation of lipid peroxyl radicals, amplification of membrane damage); and termination (neutralization by antioxidants like GPX4 and vitamin E)[1][5][7][8]. Disruption of the antioxidant defenses or iron/lipid homeostasis catalyzes ferroptotic cell death. Ferroptosis and its core pathway, lipid peroxidation, play crucial roles in many diseases, notably cancer, neurodegeneration, and cardiovascular conditions, making them promising therapeutic avenues but not classical single-gene or protein targets[3][6][9][10]. Drugs may target enzymes (such as GPX4), iron homeostasis, or the lipid peroxidation process itself; several small molecules can induce or inhibit ferroptosis for therapeutic aims[4][6][9]. Biomarkers such as malondialdehyde, 4-hydroxynonenal, and gene/protein panels are used for efficacy monitoring or patient selection[3][4][7]. There are significant safety challenges, including unintended damage to non-target tissues and risks of oxidative stress[4][10]. In summary, "Ferroptosis Pathway / Lipid Peroxidation Pathway" represents a complex process rather than a classical therapeutic target; for specific interventions, focus is usually placed on key pathway regulators such as GPX4, system Xc^−^, or iron metabolism components[6][10].

Other names

Ferroptosis signalingLipid peroxidation pathwayIron-dependent cell death pathway

Induction of ferroptosis (increase iron and lipid peroxidation, inhibit antioxidant defense, e.g. GPX4 inhibition)[6] - Inhibition of ferroptosis (antioxidants, iron chelators, GPX4 activation)[4]