Targeting Ferroptosis-associated Histone Acylation for Amelioration of Neurological Disease

Ferroptosis is an iron-dependent, lipid peroxidation-driven form of programmed cell death. There is substantial evidence supporting the critical role of ferroptosis in multiple neurological diseases, including stroke, Alzheimer's disease, Parkinson's disease, epilepsy, and traumatic brain injury. Histone acylation, an important epigenetic mechanism, effectively regulates ferroptosis. To date, the regulation of ferroptosis by histone acylation in neurological diseases has rarely been summarized. Therefore, this review discusses the key mechanisms by which histone acylation regulates ferroptosis, including iron metabolism, antioxidant defense, and lipid peroxidation. Additionally, we summarize the latest advances in understanding the role of histone acylation in ferroptosis and its relation to the emerging hallmarks of neurological diseases. Furthermore, we provide the prospect of targeting key regulatory factors of histone acylation, such as writers, erasers, and readers, for potential therapeutic strategies to ameliorate neurological diseases.