Glycosylation in neuroinflammation: mechanisms, implications, and therapeutic strategies for neurodegenerative diseases.

Neuroinflammation is a key pathological mechanism underlying neurodegenerative diseases, and intricately interacts with protein glycosylation. Emerging evidence suggests that aberrant glycosylation disrupts immune homeostasis, activates microglia, and promotes the release of inflammatory mediators, thereby exacerbating neuroinflammatory responses. In addition, the inflammatory microenvironment can further dysregulate glycosylation patterns, creating a vicious cycle that amplifies disease pathology. Although the regulatory role of glycosylation in neuroinflammation associated with neurodegenerative diseases has been recognized, the precise molecular and cellular mechanisms remain incompletely understood. This review systematically examines the complex crosstalk between glycosylation and neuroinflammation, with a particular focus on the critical roles of glycosylation in key neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. We explore how glycosylation abnormalities contribute to disease pathogenesis through effects on immune recognition, protein aggregation, and cellular functions. Understanding the molecular underpinnings of these diseases may pave the way for the development of therapeutic strategies targeting glycosylation pathways, ultimately improving clinical outcomes for patients.