Sialylation in the nervous system: Functions and mechanisms

作者：Kate Koles, Elena Repnikova, Boris Novikov, Vladislav M. Panin · 发表于：Journal of Biological Chemistry · 年份：2026 · DOI：10.1016/j.jbc.2026.111288 · 被引用次数：1 · 研究领域：Glycosylation and Glycoproteins Research、Neurogenesis and neuroplasticity mechanisms、Proteoglycans and glycosaminoglycans research

Glycoprotein sialylation represents a critical posttranslational modification with diverse biological roles in animals. This review explores its multifaceted functions in the nervous system, with particular emphasis on neurophysiology, homeostasis, and associated neurological disorders. The sialylation pathway modulates key neural processes through effects on glycoprotein stability, localization, activity, and molecular interactions. Examples include its crucial role in the regulation of neuronal excitability by modulating the functions of voltage-gated ion channels. Recent studies have uncovered remarkably rapid, activity-dependent changes in synaptic sialylation, suggesting dynamic sialylation-mediated regulation of neural transmission and highlighting the importance of neuraminidases in these processes. Beyond synaptic function, sialylation mediates neuron-glia interactions through multiple mechanisms. It modulates immune functions regulated by siglecs and complement pathways while controlling microglial activation and neuroinflammation. The critical importance of proper sialylation is underscored by severe neurological manifestations associated with genetic defects in the sialylation pathway, including cognitive impairment, ataxia, and epilepsy. Furthermore, aberrant sialylation of glycoproteins and gangliosides has been implicated in neurodegenerative diseases (Alzheimer's and Parkinson's), brain cancers, and psychiatric disorders including schizophrenia and autism. Prec...