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alpha-Mangostin, a polyphenolic xanthone derivative from mangosteen, attenuates beta-amyloid oligomers-induced neurotoxicity by inhibiting amyloid aggregation

cappuccinolin1 添加于 2011-10-19 20:52 | 1957 次阅读 | 0 个评论

作者
Wang Y, Xia Z, Xu JR, Wang YX, Hou LN, Qiu Y, Chen HZ
摘要
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of beta-sheet-rich amyloid oligomers or fibrils which are associated with cellular toxicity in the brain. Inhibition of Abeta aggregation could be a viable therapeutic strategy for slowing and/or preventing the progress of AD. Here we reported that alpha-mangostin (alpha-M), a polyphenolic xanthone derivative from mangosteen, concentration-dependently attenuated the neurotoxicity induced by Abeta-(1-40) or Abeta-(1-42) oligomers (EC(50) = 3.89 nM, 4.14 nM respectively) as observed by decreased cell viability and impaired neurite outgrowth in primary rat cerebral cortical neurons. Molecular docking and dynamics simulations demonstrated that alpha-M could potentially bind to Abeta and stabilize alpha-helical conformation. alpha-M was found to directly dissociate Abeta-(1-40) and Abeta-(1-42) oligomers by blotting with oligomer-specific antibodies. ThioflavinT fluorescence assay and electron microscopy imaging further demonstrated that alpha-M blocked the fibril formation as well as disturbed the pre-formed fibrils. Taken together, our results indicate that alpha-M is capable to inhibit and dissociate the Abeta aggregation, which could contribute to its effect of attenuating Abeta oligomers-induced neurotoxicity. Thus, alpha-M could be a great potential candidate for AD treatment.
详细资料
- 文献种类:期刊
- 期刊名称: Neuropharmacology
- 期刊缩写: Neuropharmacology
- 期卷页: 2011年
- 地址: Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China
- ISBN: 0028-3908
- 备注:PMID:21958557
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alpha-Mangostin, a polyphenolic xanthone derivative from mangosteen, attenuates beta-amyloid oligomers-induced neurotoxicity by inhibiting amyloid agg
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