College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China; Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.
Carbohydr Polym. 2023 Jan 1;299:120176. doi: 10.1016/j.carbpol.2022.120176. Epub 2022 Sep 30.
Tau spreading in Alzheimer's disease is mediated by cell surface heparan sulfate (HS). As a class of sulfated polysaccharides, fucoidans might compete with HS to bind tau, resulting in the cessation of tau spreading. The structural determinants of fucoidans for competition with HS binding to tau are not well understood. Sixty previously prepared fucoidans/glycans with different structural determinants were used to determine their binding abilities to tau using SPR and AlphaLISA. Finally, it was found that fucoidans had two fractions (sulfated galactofucan (SJ-I) and sulfated heteropolysaccharide (SJ-GX-3)), which exhibited strong binding abilities than heparin. Tau cellular uptake assays using wild type mouse lung endothelial cell lines were performed. It was shown SJ-I and SJ-GX-3 inhibited tau-cell interaction and tau cellular uptake, suggesting that fucoidans might be good candidates for inhibiting tau spreading. NMR titration mapped fucoidans binding sites, which could provide the theoretical basis for the design of tau spreading inhibitors.
阿尔茨海默病中的 tau 扩散是由细胞表面硫酸乙酰肝素 (HS) 介导的。作为一类硫酸多糖，岩藻聚糖可能与 HS 竞争结合 tau，从而阻止 tau 扩散。然而，岩藻聚糖与 HS 竞争结合 tau 的结构决定因素尚不清楚。本研究使用 60 种先前制备的具有不同结构决定因素的岩藻聚糖/聚糖，使用 SPR 和 AlphaLISA 来确定它们与 tau 的结合能力。最后发现，岩藻聚糖有两个分数（硫酸半乳聚糖 (SJ-I) 和硫酸杂多糖 (SJ-GX-3)），它们与肝素相比表现出更强的结合能力。使用野生型小鼠肺内皮细胞系进行 tau 细胞摄取实验。结果表明 SJ-I 和 SJ-GX-3 抑制 tau-细胞相互作用和 tau 细胞摄取，这表明岩藻聚糖可能是抑制 tau 扩散的良好候选物。NMR 滴定法定位了岩藻聚糖的结合位点，这为 tau 扩散抑制剂的设计提供了理论基础。
