Ferroptosis in Neurological Diseases

Abstract

Ferroptosis is mechanism for non-apoptotic, iron-dependent, oxidative cell death that is characterized by glutathione consumption and lipid peroxides accumulation. Ferroptosis is crucially involved in neurological diseases, including neurodegeneration, stroke and neurotrauma. This review provides detailed discussions of the ferroptosis mechanisms in these neurological diseases. Moreover, it summarizes recent drugs that target ferroptosis for neurological disease treatment. Furthermore, it compares the differences and relationships among the various cell death mechanisms involved in neurological diseases. Elucidating the ferroptosis role in the brain can improve the understanding of neurological disease mechanism and provide potential prevention and treatment interventions for acute and chronic neurological diseases.

Keywords: ferroptosis; inhibitors; iron; neurodegeneration; stroke.

FIGURE 1

The related ferroptosis mechanisms in neurological diseases. The drugs with red box are ferroptosis inducer and the drugs with green box are ferroptosis inhibitor. AA, arachidonic acid; AdA, adrenic acid; ACSL4, acyl-CoA synthetase long-chain family member 4; AOA, amino acetate; α-KG, α ketoglutarate; BSO, buthionine sulfoximine; 2,2-BP, 2,2-bipyridyl; β-ME, β-mercaptoethanol; CO, carbon monoxide; CoQ 10, Coenzyme Q10; CP, ceruloplasmin; DMT1, divalent metal transporter 1; FAC, ferric citrate; FINO2, 1, 2-dioxolane; FSP-1, Ferroptosis-suppressor-protein 1; GCL, glutamate cysteine ligase; GLS2, glutaminase 2; Glu, glutamate; GSS, glutathione synthetase; GSSG, oxidized GSH; Hb, hemoglobin; HIF, hypoxia-inducible factor; 4-HNE, 4-hydroxynonenal; HO-1, heme oxygenase 1; Lip-1, liproxstatin-1; LPCAT3, lysophosphatidylcholine acyltransferase 3; NAA, neutral amino acids; NAC, N-acetylcysteine; NOX, nitrogen oxide; 2-OG, 2-oxoglutarate; PPP, pentose phosphate pathway; RSL3, RAS-selective lethal 3; SAS, sulfasalazine; STEAP3, 6-transmembrane epithelial antigen of the prostate 3.