The Role of Iron Metabolism, Lipid Metabolism, and Redox Homeostasis in Alzheimer's Disease: from the Perspective of Ferroptosis

Abstract

In the development of Alzheimer's disease (AD), cell death is common. Novel cell death form-ferroptosis is discovered in recent years. Ferroptosis is an iron-regulated programmed cell death mechanism and has been identified in AD clinical samples. Typical characteristics of ferroptosis involve the specific changes in cell morphology, iron-dependent aggregation of reactive oxygen species (ROS) and lipid peroxides, loss of glutathione (GSH), inactivation of glutathione peroxidase 4 (GPX4), and a unique group of regulatory genes. Increasing evidence demonstrates that ferroptosis may be associated with neurological dysfunction in AD. However, the underlying mechanisms have not been fully elucidated. This article reviews the potential role of ferroptosis in AD, the involvement of ferroptosis in the pathological progression of AD through the mechanisms of iron metabolism, lipid metabolism, and redox homeostasis, as well as a range of potential therapies targeting ferroptosis for AD. Intervention strategies based on ferroptosis are promising for Alzheimer's disease treatment at present, but further researches are still needed.

Keywords: Alzheimer’s disease; Ferroptosis; Iron metabolism; Lipid metabolism; Redox homeostasis.