Abstract
Succinylation is a post-translational modification that occurs on lysine residues and is mediated by succinyl-CoA, an intermediate of the tricarboxylic acid (TCA) cycle. It can significantly affect protein conformation, activity, stability, and interactions with other molecules, thereby participating in the regulation of important biological processes such as cellular metabolism, energy homeostasis, and signaling pathways. In recent years, increasing evidence has shown that succinylation plays a key role in central nervous system (CNS) diseases, particularly in Alzheimer’s disease, stroke, subarachnoid hemorrhage (SAH), and microglial glioma. Succinylation modification participates in neuronal injury and repair processes by influencing mitochondrial function, oxidative stress, autophagic flux, immune responses, and inflammation. A systematic description of the enzymatic and non-enzymatic regulatory mechanisms of succinylation, along with a summary of its functional roles and potential therapeutic value in different CNS diseases, especially the role of desuccinylases such as sirtuin 5 (SIRT5) as potential therapeutic targets, can provide a new theoretical basis and conceptual support for understanding the pathogenesis of CNS diseases and developing targeted intervention strategies. Future research should further clarify the core characteristics of disease-specific succinylation profiles and the integration patterns of multi-omics data, elucidate the molecular mechanisms of crosstalk among post-translational modifications, and promote the clinical translation of biomarkers and precision therapeutic drugs based on succinylation pathways.