期刊
MOLECULES
卷 22, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/molecules22101651
关键词
5-hydroxycyclopenicillone; beta-amyloid; Alzheimer's disease; sponge-associated fungus; oligomer
资金
- Natural Science Foundation of Zhejiang Province [LY15H310007]
- Applied Research Project on Nonprofit Technology of Zhejiang Province [2016C37110]
- National Natural Science Foundation of China [U1503223, 21576199, 81673407, 41776168]
- Ningbo International Science and Technology Cooperation Project [2014D10019]
- Ningbo municipal innovation team of life science and health [2015C110026]
- Ningbo Sci & Tech Project for Common Wealth [2015C10026, 2017C10016, 2017C50042]
- National 111 Project of China
- Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Development Fund
- K. C. Wong Magna Fund in Ningbo University
The oligomer of beta-amyloid (A beta) is considered the main neurotoxin in Alzheimer's disease (AD). Therefore, the inhibition of the formation of A beta oligomer could be a target for AD therapy. In this study, with the help of the dot blotting assay and transmission electronic microscopy, it was have discovered that 5-hydroxycyclopenicillone, a cyclopentenone recently isolated from a sponge-associated fungus, effectively reduced the formation of A beta oligomer from A beta peptide in vitro. Molecular dynamics simulations suggested hydrophobic interactions between 5-hydroxycyclopenicillone and A beta peptide, which might prevent the conformational transition and oligomerization of A beta peptide. Moreover, A beta oligomer pre-incubated with 5-hydroxycyclopenicillone was less toxic when added to neuronal SH-SY5Y cells compared to the normal A beta oligomer. Although 5-hydroxycyclopenicillone is not bioavailable in the brain in its current form, further modification or encapsulation of this chemical might improve the penetration of 5-hydroxycyclopenicillone into the brain. Based on the current findings and the anti-oxidative stress properties of 5-hydroxycyclopenicillone, it is suggested that 5-hydroxycyclopenicillone may have potential therapeutic efficacy in treating AD.
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