Progress of p53 Involvement in Central Nervous System Diseases and Targeted Drug Discovery

ABSTRACT p53 plays a critical role in the pathogenesis of central nervous system (CNS) diseases, including neurodegenerative diseases, stroke, and neurodevelopmental disorders. Recent studies have shown that p53 regulates pathological processes such as apoptosis, ferroptosis, neuroinflammation, mitochondrial dysfunction, DNA damage, and synaptic dysfunction through complex molecular pathways. Preclinical studies have demonstrated that pharmacological inhibition or knockdown of p53 exerts neuroprotective effects, suggesting its potential therapeutic value. This review systematically summarizes the mechanisms of p53 in CNS diseases and the associated signaling pathways involved in these pathological processes. Additionally, p53‐related intervention strategies in CNS diseases and challenges to the development of p53‐targeted drugs are summarized, aiming to provide new insights for therapeutic treatment.