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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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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. |
format | Online Article Text |
id | pubmed-6151400 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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