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Molecules 2017, 22(10), 1651; doi:10.3390/molecules22101651

5-Hydroxycyclopenicillone Inhibits β-Amyloid Oligomerization and Produces Anti-β-Amyloid Neuroprotective Effects In Vitro

1
Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Ningbo University, Ningbo 315211, China
2
Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China
3
Key Laboratory of Industrial Fermentation Microbiology of Education, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China
4
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093, USA
*
Authors to whom correspondence should be addressed.
Received: 16 August 2017 / Revised: 20 September 2017 / Accepted: 29 September 2017 / Published: 1 October 2017
(This article belongs to the Special Issue 25th Anniversary of the Amyloid Hypothesis and Alzheimer Disease)
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Abstract

The oligomer of β-amyloid (Aβ) is considered the main neurotoxin in Alzheimer’s disease (AD). Therefore, the inhibition of the formation of Aβ 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 Aβ oligomer from Aβ peptide in vitro. Molecular dynamics simulations suggested hydrophobic interactions between 5-hydroxycyclopenicillone and Aβ peptide, which might prevent the conformational transition and oligomerization of Aβ peptide. Moreover, Aβ oligomer pre-incubated with 5-hydroxycyclopenicillone was less toxic when added to neuronal SH-SY5Y cells compared to the normal Aβ 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. View Full-Text
Keywords: 5-hydroxycyclopenicillone; β-amyloid; Alzheimer’s disease; sponge-associated fungus; oligomer 5-hydroxycyclopenicillone; β-amyloid; Alzheimer’s disease; sponge-associated fungus; oligomer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Zhao, J.; Liu, F.; Huang, C.; Shentu, J.; Wang, M.; Sun, C.; Chen, L.; Yan, S.; Fang, F.; Wang, Y.; Xu, S.; Naman, C.B.; Wang, Q.; He, S.; Cui, W. 5-Hydroxycyclopenicillone Inhibits β-Amyloid Oligomerization and Produces Anti-β-Amyloid Neuroprotective Effects In Vitro. Molecules 2017, 22, 1651.

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