Driving factors of neuronal ferroptosis

Ferroptosis is an oxidative form of iron-dependent cell death characterized by the accumulation of lipid peroxides on membranes. Iron and lipids containing polyunsaturated fatty acids are essential for this process. Ferroptosis is central to several neurological diseases and underlies the importance of balanced iron and polyunsaturated fatty acid metabolism in the brain, particularly in neurons. Here, we reflect on the potential links between neuronal physiology and the accumulation of iron and peroxidated lipids, the mechanisms neurons use to protect themselves from ferroptosis, and the relationship between pathogenic protein deposition and ferroptosis in neurodegenerative disease. We propose that the unique physiology of neurons makes them especially vulnerable to ferroptosis.