The role of ferroptosis in Alzheimer's disease: Mechanisms and therapeutic potential (Review)

Abstract

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by insidious onset and progressive symptom deterioration. It extends beyond a simple aging process, involving irreversible and progressive neurological degeneration that impairs brain function through multiple etiologies. Iron dysregulation is implicated in the pathophysiology of AD; however, the precise mechanisms remain unclear. Additionally, vitamin E and selenium are key in regulating ferroptosis through their antioxidant properties. The present review examined the mechanistic pathways by which ferroptosis contributes to AD, the regulatory roles of vitamin E, selenium, ferrostatin‑1, N‑acetylcysteine and curcumin, and their potential as therapeutic agents to mitigate neurodegeneration.

Keywords: Alzheimer's disease; drug; ferroptosis; pathophysiology.

Figure 1.

Molecular mechanisms of ferroptosis primarily involve lipid, iron and amino acid metabolism. Made with Figdraw.com. SLC7A11, solute carrier family 7a member 11; GGC, γ-glutamylcysteine; GSH, glutathione; GPX, glutathione peroxidase family; RSL, Ras-selective lethal small molecule; PL-PUFA-OOH, lipid peroxides; TCA, tricarboxylic acid; LOX, lipoxygenase; LPCAT, lysophosphatidylcholine acyltransferase; ACSL, acyl-CoA synthetase long-chain family; ACAC, acetyl-CoA carboxylase; VDAC, voltage-dependent anion channel); NCOA4, Nuclear receptor coactivator 4; Fpn, ferroportin.

Figure 2.

Potential ferroptosis inhibitors in the treatment of Alzheimer's disease. Made with Figdraw.com. SLC7A11, solute carrier family 7a member 11; HMG, 3-hydroxy-3-methylglutaryl; MVA, mevalonate; IPP, isopentenyl pyrophosphate; CoQ₁₀, coenzyme Q10; ROS, reactive oxygen species; GSH, Glutathione; GPX, glutathione peroxidase family; BSO, buthionine sulfoximine; TF, transferrin.