Origins of nervous tissue susceptibility to ferroptosis

Ferroptosis is a newly defined form of programmed cell death. It possesses unique processes of cell demise, cytopathological changes, and independent signal regulation pathways. Ferroptosis is considered to be deeply involved in the development of many diseases, including cancer, cardiovascular diseases, and neurodegeneration. Intriguingly, why cells in certain tissues and organs (such as the central nervous system, CNS) are more sensitive to changes in ferroptosis remains a question that has not been carefully discussed. In this Holmesian review, we discuss lipid composition as a potential but often overlooked determining factor in ferroptosis sensitivity and the role of polyunsaturated fatty acids (PUFAs) in the pathogenesis of several common human neurodegenerative diseases. In subsequent studies of ferroptosis, lipid composition needs to be given special attention, as it may significantly affect the susceptibility of the cell model used (or the tissue studied).