Advancements in mechanisms of astrocytic regulation of programmed neuron death in epileptogenesis

The pathogenesis of epilepsy is complex, in which, programmed neuron death plays a crucial role. Recent studies have revealed that astrocytes can directly or indirectly induce neuronal death through multiple mechanisms, including neuronal apoptosis, necroptosis, and ferroptosis, thereby promoting the progression of epilepsy. This review summarizes the pathological transformation of astrocytes into reactive subtypes in epilepsy, including A1-type reactive astrocytes and lipid-accumulated reactive astrocytes. It highlights their vital role in programmed neuronal death such as apoptosis, ferroptosis, and necroptosis by modulating glutamate metabolism, iron metabolism, lipid metabolism, and inflammatory responses. The aim is to provide a novel foundation for development of new anti seizure medicaments that target either reactive astrocytes or neuronal death pathways.