Journal Article

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

Cui, Wei, Fang, Fang, Xu, Shujun, Liu, Fufeng, Wang, Qinwen, Shentu, Jieyi, Wang, Yuanyuan, Wang, Minjun, Zhao, Jiaying, Huang, Chunhui, Sun, Chenkai, He, Shan, Naman, C., Chen, Liping, Yan, Sicheng

2017

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: 5-hydroxycyclopenicillone / Alzheimer Disease - drug therapy / Alzheimer’s disease / Amyloid beta-Peptides - antagonists & inhibitors / Cell Line, Tumor / Cell Survival - drug effects / Cyclopentanes - chemistry / Cyclopentanes - pharmacology / Fungi - chemistry / Humans / Molecular Dynamics Simulation / Neurons - drug effects / Neurons - pathology / Neuroprotective Agents - chemistry / Neuroprotective Agents - pharmacology / Neuroprotective Agents - therapeutic use / oligomer / Peptides / sponge-associated fungus / β-amyloid