Targeting O-GlcNAcylation: Novel Therapeutic Strategies for Neurological Disease

GlcNAcylation is a crucial post-translational modification. O-GlcNAcylation represents a dynamic monosaccharide modification that exhibits complex crosstalk with other post-translational modifications. It is ubiquitously present in nuclear, cytoplasmic, and mitochondrial proteins, participating in fundamental physiological processes such as cell adhesion and signal transduction. O-GlcNAcylation is particularly abundant in the brain, where it plays critical roles in nervous system development, synaptic plasticity, and energy metabolism. Functioning as both a nutrient sensor and signal integrator, O-GlcNAcylation holds significant importance in both the physiological and pathological processes of the nervous system. The development of pharmacological agents targeting O-GlcNAcylation has emerged as a major research focus. These agents have demonstrated therapeutic potential in animal models, including improving cognitive function, attenuating neuroinflammation, and inhibiting pathological protein aggregation. This review focuses on the roles of O-GlcNAc modification in neurological disorders and summarizes current drug development efforts targeting these conditions, aiming to provide novel perspectives for future research.