Ferroptosis, a Distinct Form of Cell Death, and Research Progress on Its Modulators

Abstract

Ferroptosis, an iron-dependent and lipid peroxidation-driven mode of regulated cell death, holds significant pathological significance. Its dysregulation manifests in dual facets: inhibition promotes tumorigenesis, whereas overactivation aggravates neurological disorders and organ injury. This paper systematically reviews the core molecular mechanisms of ferroptosis and provides a comprehensive summary of recent advances in its modulators: inducers classified by targets (GPX4 axis, iron metabolism, lipid metabolism, and GPX4-independent antioxidant pathways) and inhibitors classified by source (synthetic and natural). It places a particular focus on summarizing and analyzing the optimization strategies, mechanisms of action, existing limitations, and future directions for novel ferroptosis modulators, to offer valuable insights for future drug development targeting ferroptosis.