期刊
FRONTIERS IN PHARMACOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2020.553579
关键词
amyloid-beta; oligomers; Alzheimer's disease; frondoside A; Caenorhabditis elegans
资金
- Royal Golden Jubilee (RGJ) Ph.D. scholarship [PHD/0004/2558]
- Faculty of Science, Mahidol University
- NIH Office of Research Infrastructure Programs [P40 OD010440]
Oligomeric assembly of Amyloid-beta (A beta) is the main toxic species that contribute to early cognitive impairment in Alzheimer's patients. Therefore, drugs that reduce the formation of A beta oligomers could halt the disease progression. In this study, by using transgenicCaenorhabditis elegansmodel of Alzheimer's disease, we investigated the effects of frondoside A, a well-known sea cucumberCucumaria frondosasaponin with anti-cancer activity, on A beta aggregation and proteotoxicity. The results showed that frondoside A at a low concentration of 1 mu M significantly delayed the worm paralysis caused by A beta aggregation as compared with control group. In addition, the number of A beta plaque deposits in transgenic worm tissues was significantly decreased. Frondoside A was more effective in these activities than ginsenoside-Rg3, a comparable ginseng saponin. Immunoblot analysis revealed that the level of small oligomers as well as various high molecular weights of A beta species in the transgenicC. eleganswere significantly reduced upon treatment with frondoside A, whereas the level of A beta monomers was not altered. This suggested that frondoside A may primarily reduce the level of small oligomeric forms, the most toxic species of A beta. Frondoside A also protected the worms from oxidative stress and rescued chemotaxis dysfunction in a transgenic strain whose neurons express A beta. Taken together, these data suggested that low dose of frondoside A could protect against A beta-induced toxicity by primarily suppressing the formation of A beta oligomers. Thus, the molecular mechanism of how frondoside A exerts its anti-A beta aggregation should be studied and elucidated in the future.
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