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一种能够抑制 Aβ42 聚集和减轻 BV-2 小胶质细胞炎症反应的低聚甘露糖醛酸唾液酸缀合物。

An Oligomannuronic Acid-Sialic Acid Conjugate Capable of Inhibiting Aβ42 Aggregation and Alleviating the Inflammatory Response of BV-2 Microglia.

机构信息

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.

Division of Histology and Embryology, International Joint Laboratory for Embryonic Development and Prenatal Medicine, Medical College, Jinan University, Guangzhou 510632, China.

出版信息

Int J Mol Sci. 2021 Nov 15;22(22):12338. doi: 10.3390/ijms222212338.

DOI:10.3390/ijms222212338
PMID:34830217
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8621211/
Abstract

Oligomannuronic acid (MOS) from seaweed has antioxidant and anti-inflammatory activities. In this study, MOS was activated at the terminal to obtain three different graft complexes modified with sialic acid moiety (MOS-Sia). The results show that MOS-Sia addition can reduce the β-structure formation of Aβ42, and the binding effect of MOS-Sia3 is more obvious. MOS-Sia conjugates also have a better complexing effect with Ca while reducing the formation of Aβ42 oligomers in solutions. MOS-Sia3 (25-50 μg/mL) can effectively inhibit the activation state of BV-2 cells stimulated by Aβ42, whereas a higher dose of MOS-Sia3 (>50 μg/mL) can inhibit the proliferation of BV-2 cells to a certain extent. A lower dose of MOS-Sia3 can also inhibit the expression of IL-1β, IL-6, TNF-α, and other proinflammatory factors in BV-2 cells induced by Aβ42 activation. In the future, the MOS-Sia3 conjugate can be used to treat Alzheimer's disease.

摘要

寡甘露糖醛酸(MOS)来自海藻,具有抗氧化和抗炎活性。在这项研究中,MOS 在末端被激活,得到了三种不同的带有唾液酸部分的接枝复合物(MOS-Sia)。结果表明,MOS-Sia 的添加可以减少 Aβ42 的 β-结构形成,并且 MOS-Sia3 的结合效果更为明显。MOS-Sia 缀合物与 Ca 也具有更好的络合作用,同时减少溶液中 Aβ42 低聚物的形成。MOS-Sia3(25-50μg/mL)可以有效抑制 Aβ42 刺激的 BV-2 细胞的激活状态,而较高剂量的 MOS-Sia3(>50μg/mL)在一定程度上可以抑制 BV-2 细胞的增殖。较低剂量的 MOS-Sia3 还可以抑制 Aβ42 激活诱导的 BV-2 细胞中 IL-1β、IL-6、TNF-α 等促炎因子的表达。未来,MOS-Sia3 缀合物可用于治疗阿尔茨海默病。

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