BioMedicine Design, Discovery and Early Development, Pfizer Research and Development, 610 Main Street, Cambridge, MA 02139, USA.
Analytical Research and Development, Biotherapeutics Pharmaceutical Sciences, Pfizer Inc., Andover, MA 01810, USA.
Int J Mol Sci. 2024 Nov 7;25(22):11962. doi: 10.3390/ijms252211962.
Glycan structures of glycoproteins and glycolipids on the surface glycocalyx and luminal sugar layers of intracellular membrane compartments in human cells constitute a key interface between intracellular biological processes and external environments. Sialic acids, a class of alpha-keto acid sugars with a nine-carbon backbone, are frequently found as the terminal residues of these glycoconjugates, forming the critical components of these sugar layers. Changes in the status and content of cellular sialic acids are closely linked to many human diseases such as cancer, cardiovascular, neurological, inflammatory, infectious, and lysosomal storage diseases. The molecular machineries responsible for the biosynthesis of the sialylated glycans, along with their biological interacting partners, are important therapeutic strategies and targets for drug development. The purpose of this article is to comprehensively review the recent literature and provide new scientific insights into the mechanisms and therapeutic implications of sialylation in glycoproteins and glycolipids across various human diseases. Recent advances in the clinical developments of sialic acid-related therapies are also summarized and discussed.
糖蛋白和糖脂的聚糖结构位于人细胞表面糖萼和细胞内膜隔室的腔侧糖层，构成了细胞内生物过程与外部环境之间的关键界面。唾液酸是一类具有九碳骨架的α-酮酸糖，经常作为这些糖缀合物的末端残基出现，形成这些糖层的关键成分。细胞唾液酸的状态和含量的变化与人的许多疾病密切相关，如癌症、心血管、神经、炎症、感染和溶酶体贮积病。负责唾液酸化聚糖生物合成的分子机制及其生物相互作用伙伴是药物开发的重要治疗策略和靶点。本文的目的是全面综述近期文献，为糖蛋白和糖脂中唾液酸化在各种人类疾病中的机制和治疗意义提供新的科学见解。还总结和讨论了唾液酸相关治疗的临床进展。
