Glycosylation in neurological disorders: Mechanisms, crosstalk, and therapeutic implications

Neurological disorders pose a major global health challenge for complicated pathogenesis and a lack of effective curative treatments. As a post-translational modification, glycosylation has emerged as a multifunctional regulator in the nervous system, influencing key processes including receptor activation, cell adhesion, and immune surveillance. Its dysfunction is increasingly recognized as a shared mechanism across various neurological disorders. This review synthesizes the molecular mechanisms of glycosylation within a novel framework of four neurological disorder categories: neurodevelopmental disorders, proteostasis disorders, neuroimmunological disorders, and acute nerve injuries. Furthermore, we advance the concept of glycosylation as an integrator of mechanistic crosstalk and demonstrate its pivotal role in bridging and amplifying intertwined pathological cascades. This integrative perspective aims to reframe the understanding of disease pathogenesis and inspire innovative diagnostic paradigms and therapeutic strategies.