Cheng Shenglan, Xiao Bo, Luo Zhaohui
Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Xiangya School of Medicine, Central South University, Changsha, 410013, China.
Transl Neurodegener. 2025 Sep 22;14(1):47. doi: 10.1186/s40035-025-00506-4.
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.
神经炎症是神经退行性疾病潜在的关键病理机制，并且与蛋白质糖基化存在复杂的相互作用。新出现的证据表明，异常糖基化会破坏免疫稳态，激活小胶质细胞，并促进炎症介质的释放，从而加剧神经炎症反应。此外，炎症微环境会进一步扰乱糖基化模式，形成一个放大疾病病理过程的恶性循环。尽管糖基化在与神经退行性疾病相关的神经炎症中的调节作用已得到认可，但其精确的分子和细胞机制仍未完全明了。本综述系统地研究了糖基化与神经炎症之间的复杂相互作用，特别关注糖基化在关键神经退行性疾病（包括阿尔茨海默病、帕金森病、多发性硬化症和肌萎缩侧索硬化症）中的关键作用。我们探讨了糖基化异常如何通过影响免疫识别、蛋白质聚集和细胞功能来促进疾病发病机制。了解这些疾病的分子基础可能为开发针对糖基化途径的治疗策略铺平道路，最终改善患者的临床结局。
