期刊
ACS APPLIED MATERIALS & INTERFACES
卷 12, 期 37, 页码 41167-41176出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.0c14292
关键词
Alzheimer's disease; amyloid-beta protein; ulvan; reactive oxygen species; inhibition; disaggregation
资金
- National Natural Science Foundation of China [21878234, 21908165, 21576199]
- Natural Science Foundation of Tianjin from the Tianjin Municipal Science and Technology Commission [18JCZDJC33000]
The abnormal folding and aggregation of amyloid-beta protein (A beta) is the main reason for the occurrence and development of Alzheimer's disease (AD). The discovery of novel inhibitors against A beta aggregation is still the current research focus. Herein, we report the inhibitory effect of ulvan, an acidic polysaccharide from green algae of the genus Ulva, against A beta fibrillation using thioflavin T (ThT) fluorescence and atomic force microscopy (AFM) assays. It is shown that ulvan effectively inhibits A beta fibrillogenesis in a concentration-dependent manner and actively inhibits the formation of A11-reactive A beta oligomers, the most toxic A beta species. The circular dichroism spectrum reveals that ulvan blocks the conformational transition of A beta 40 from the initial random coil to a beta-sheet structure, but it only delays the conformational transition of A beta 42. It is also found that ulvan greatly reduces A beta-induced cytotoxicity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, ulvan effectively downregulates intracellular reactive oxygen species production and protects PC12 cells from the damage caused by A beta fibrillation. Moreover, ulvan disaggregates preformed mature fibrils into off-pathway oligomers and greatly decreases their associated cytotoxicity, as revealed using ThT fluorescence, AFM, MTT, and dot-blotting assays. The above results not only fully describe the inhibitory effect of ulvan on A beta fibrillation and its related cytotoxicity but also provide novel ideas for the development of functional food ingredients from seaweed to treat AD.
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