Fucoidans inhibited tau interaction and cellular uptake
Fucoidans inhibited tau interaction and cellular uptake
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DOI：
10.1016/j.carbpol.2022.120176
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发表时间：
2022-10-05
影响因子：
11.2
通讯作者：
Zhang，Fuming
中科院分区：
文献类型：
--
作者：
Jin，Weihua;Lu，Chenghui;Zhang，Fuming
Tau在阿尔茨海默病中的扩散是由细胞表面硫酸肝素（HS）介导的。岩藻多糖作为一类硫酸酸化多糖，可能与HS竞争结合tau蛋白，导致tau蛋白扩散停止。岩藻蛋白与HS结合tau蛋白竞争的结构决定因素尚不清楚。使用SPR和AlphaLISA测定了60种先前制备的具有不同结构决定因素的岩藻多糖/聚糖与tau蛋白的结合能力。最后发现岩藻多糖有两个组分（硫酸半乳岩藻聚糖（sj - 1）和硫酸杂多糖（SJ-GX-3）），它们比肝素具有更强的结合能力。利用野生型小鼠肺内皮细胞系进行Tau细胞摄取测定。结果表明，sj - 1和SJ-GX-3抑制tau细胞相互作用和tau细胞摄取，表明岩藻样蛋白可能是抑制tau扩散的良好候选者。核磁共振滴定法绘制了岩藻胶结合位点，可为tau扩散抑制剂的设计提供理论依据。
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.