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

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 discove...

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Autores principales: Zhao, Jiaying, Liu, Fufeng, Huang, Chunhui, Shentu, Jieyi, Wang, Minjun, Sun, Chenkai, Chen, Liping, Yan, Sicheng, Fang, Fang, Wang, Yuanyuan, Xu, Shujun, Naman, C. Benjamin, Wang, Qinwen, He, Shan, Cui, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151400/
https://www.ncbi.nlm.nih.gov/pubmed/28974023
http://dx.doi.org/10.3390/molecules22101651
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author Zhao, Jiaying
Liu, Fufeng
Huang, Chunhui
Shentu, Jieyi
Wang, Minjun
Sun, Chenkai
Chen, Liping
Yan, Sicheng
Fang, Fang
Wang, Yuanyuan
Xu, Shujun
Naman, C. Benjamin
Wang, Qinwen
He, Shan
Cui, Wei
author_facet Zhao, Jiaying
Liu, Fufeng
Huang, Chunhui
Shentu, Jieyi
Wang, Minjun
Sun, Chenkai
Chen, Liping
Yan, Sicheng
Fang, Fang
Wang, Yuanyuan
Xu, Shujun
Naman, C. Benjamin
Wang, Qinwen
He, Shan
Cui, Wei
author_sort Zhao, Jiaying
collection PubMed
description 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.
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spelling pubmed-61514002018-11-13 5-Hydroxycyclopenicillone Inhibits β-Amyloid Oligomerization and Produces Anti-β-Amyloid Neuroprotective Effects In Vitro Zhao, Jiaying Liu, Fufeng Huang, Chunhui Shentu, Jieyi Wang, Minjun Sun, Chenkai Chen, Liping Yan, Sicheng Fang, Fang Wang, Yuanyuan Xu, Shujun Naman, C. Benjamin Wang, Qinwen He, Shan Cui, Wei Molecules Article 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. MDPI 2017-10-01 /pmc/articles/PMC6151400/ /pubmed/28974023 http://dx.doi.org/10.3390/molecules22101651 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhao, Jiaying
Liu, Fufeng
Huang, Chunhui
Shentu, Jieyi
Wang, Minjun
Sun, Chenkai
Chen, Liping
Yan, Sicheng
Fang, Fang
Wang, Yuanyuan
Xu, Shujun
Naman, C. Benjamin
Wang, Qinwen
He, Shan
Cui, Wei
5-Hydroxycyclopenicillone Inhibits β-Amyloid Oligomerization and Produces Anti-β-Amyloid Neuroprotective Effects In Vitro
title 5-Hydroxycyclopenicillone Inhibits β-Amyloid Oligomerization and Produces Anti-β-Amyloid Neuroprotective Effects In Vitro
title_full 5-Hydroxycyclopenicillone Inhibits β-Amyloid Oligomerization and Produces Anti-β-Amyloid Neuroprotective Effects In Vitro
title_fullStr 5-Hydroxycyclopenicillone Inhibits β-Amyloid Oligomerization and Produces Anti-β-Amyloid Neuroprotective Effects In Vitro
title_full_unstemmed 5-Hydroxycyclopenicillone Inhibits β-Amyloid Oligomerization and Produces Anti-β-Amyloid Neuroprotective Effects In Vitro
title_short 5-Hydroxycyclopenicillone Inhibits β-Amyloid Oligomerization and Produces Anti-β-Amyloid Neuroprotective Effects In Vitro
title_sort 5-hydroxycyclopenicillone inhibits β-amyloid oligomerization and produces anti-β-amyloid neuroprotective effects in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151400/
https://www.ncbi.nlm.nih.gov/pubmed/28974023
http://dx.doi.org/10.3390/molecules22101651
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