Unsaturated mannuronate oligosaccharide ameliorates β-amyloid pathology through autophagy in Alzheimer's disease cell models
Unsaturated mannuronate oligosaccharide ameliorates β-amyloid pathology through autophagy in Alzheimer's disease cell models
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不饱和甘露糖醛酸寡糖通过阿尔茨海默病细胞模型中的自噬改善β淀粉样蛋白病理学
DOI：
10.1016/j.carbpol.2020.117124
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发表时间：
2021-01-01
影响因子：
11.2
通讯作者：
Xu, Xu
中科院分区：
文献类型：
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作者：
Bi, Decheng;Yao, Lijun;Xu, Xu
不饱和甘露糖醛酸寡糖（MOS）是藻酸盐衍生的聚甘露糖醛酸（PM）的酶促解聚产物。在这项研究中，我们首次研究了MOS对阿尔茨海默病（AD）的潜在治疗作用及其在N2 a-sw细胞和3 x Tg-AD原代皮层神经元中的分子机制。我们的研究结果表明，MOS范围从甘露糖醛酸二聚体到甘露糖醛酸十一聚体（M2-M11），具有不饱和的非还原性末端结构，并具有双键和1，4-糖苷键。它显著抑制淀粉样蛋白β（A β）（1-42）寡聚体的聚集，降低A β（1-42）的表达，并降低淀粉样蛋白前体蛋白（APP）和BACE 1的水平。它促进自噬，这涉及mTOR信号通路的失活以及自噬体与溶酶体的融合。最后，自噬抑制剂阻断了MOS的抗AD作用，证实了自噬的参与。因此，海藻酸钠中的MOS可能是一种很有前途的治疗AD的营养保健品或天然药物。
Unsaturated mannuronate oligosaccharide (MOS) is an enzymatic depolymerization product from alginate-derived polymannuronate (PM). In this study, we investigated for the first time the potential therapeutic effect of MOS on Alzheimer's disease (AD) and its molecular mechanism in N2a-sw cells and 3 x Tg-AD primary cortex neurons. Our results showed that MOS ranges from mannuronate dimer to mannuronate undecamer (M2-M11) with an unsaturated nonreducing terminal structure and with a double bond and 1,4-glycosidic linkages. It significantly inhibited the aggregation of amyloid-beta (A beta)(1-42) oligomer, decreased expression of A beta(1-42) and reduced levels of amyloid precursor protein (APP) and BACE1. It promoted the autophagy, which involves the inactivation of mTOR signaling pathway and the facilitation of the fusion of autophagosomes and lysosomes. Finally, autophagy inhibitors blocked MOS' anti-AD actions, confirming the involvement of autophagy. In conclusion, MOS from seaweed alginate might be a promising nutraceutical or natural medicine for AD therapy.