The key role of the ferroptosis mechanism in neurological diseases and prospects for targeted therapy

Abstract

Neurological disorders represent a major global health concern owing to their intricate pathological processes. Ferroptosis, defined as a form of cell death that is reliant on iron, has been closely linked to various neurological conditions. The fundamental process underlying ferroptosis is defined by the excessive buildup of iron ions, which initiates lipid peroxidation processes leading to cellular demise. Neurons, as highly metabolically active cells, are susceptible to oxidative stress, and imbalances in iron metabolism can directly initiate the ferroptosis process. In neurodegenerative disorders like Alzheimer's disease and Parkinson's disease, ferroptosis driven by iron accumulation represents a fundamental pathological connection. Although the connection between ferroptosis and neurological diseases is clear, clinical application still faces challenges, such as precise regulation of iron metabolism, development of specific drugs, and assessment of efficacy. The limited comprehension of the ferroptosis mechanism hinders the development of personalized treatment approaches. Consequently, subsequent investigations must tackle these obstacles to facilitate the clinical application of ferroptosis-associated therapies in neurological disorders. This article provides a comprehensive overview of the most recent advancements regarding the underlying mechanisms of ferroptosis. Subsequently, the study investigates the mechanistic contributions of ferroptosis within the nervous system. In conclusion, we evaluate and deliberate on targeted therapeutic strategies associated with ferroptosis and neurological disorders.

Keywords: cell death; ferroptosis; medication therapy; neurological diseases; research progress.

Figure 1

Created with Biogdp.com (Jiang et al., 2025). Tf, Transferrin; Fr1, Transferrin Receptor 1; Dmt1, Divalent Metal Transporter 1; Fpn, Ferroportin; Nrf2, Nuclear Factor Erythroid 2-Related Factor 2; Otub1, Otubain 1;Slc7A11, Solute Carrier Family 7 Member 11; Slc3A2, Solute Carrier Family 3 Member 2;Ho-1, Heme Oxygenase-1; Ncoa4, Nuclear Receptor Co-Activator 4; Steap3, Six-Transmembrane Epithelial Antigen of Prostate 3; Lip, Lipid; γ – Gcs, γ-Glutamyl Cysteine Synthetase; Gssg, Oxidized Glutathione; Acsl4, Acyl-CoA Synthetase Long-Chain Family Member 4; Lpcat3, Lysophosphatidylcholine Acyltransferase 3; Lox, Lipoxygenase; Pufas, Polyunsaturated Fatty Acids; Pufa-CoA, Polyunsaturated Fatty Acyl-Coenzyme A; Pufa-Pl, Polyunsaturated Fatty Acid-Phospholipid; Pl-Oohs, Phospholipid Hydroperoxides; CoQ₁₀, Coenzyme Q₁₀; Fsp1, Ferropoptosis Suppressor Protein 1. This is a diagram of the ferroptosis mechanism. On the left side, iron metabolism is shown. The middle part involves the antioxidant system. The right side demonstrates that lipid peroxidation is related to ferroptosis. Overall, it elucidates the interactions among various metabolic pathways and associated molecules involved in the process of ferroptosis.

Figure 2

Created with Biogdp.com (Jiang et al., 2025). This diagram illustrates the associations between ferroptosis and various nervous system diseases. In the central part of the diagram, ferroptosis is labeled. The surrounding ring points out the key factors related to ferroptosis. Different sectors radiating out from the center correspond to various types of nervous system diseases. Overall, it elucidates the function and associated mechanisms of ferroptosis in the onset and progression of various neurological disorders.

Figure 3

Created with BioGDP (Jiang et al., 2025). This schematic diagram centers on the three core elements of ferroptosis (iron metabolism imbalance, lipid peroxidation, antioxidant collapse), with six categories of targeted therapeutic strategies surrounding it. Through iron chelators, antioxidants, nano-drug delivery, gene regulation, autophagy induction, and multi-pathway coordination, dynamic arrows visually display the action pathways of each therapy—from removing excessive iron ions and inhibiting the lipid oxidation storm to repairing the antioxidant barrier. Finally, cross-mechanism coordinated intervention is achieved through the interlocking of gears.