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

Title5-Hydroxycyclopenicillone Inhibits beta-Amyloid Oligomerization and Produces Anti-beta-Amyloid Neuroprotective Effects In Vitro
Publication TypeJournal Article
Year of Publication2017
AuthorsZhao J.Y, Liu F.F, Huang C.H, Shentu J.Y, Wang M.J, Sun C.K, Chen L.P, Yan S.C, Fang F., Wang Y.Y, Xu S.J, Naman C.B, Wang Q.W, He S., Cui W.
Date Published2017/10
Type of ArticleArticle
ISBN Number1420-3049
Accession NumberWOS:000414670600078
Keywords5-hydroxycyclopenicillone; aggregation; Alzheimer's disease; alzheimers-disease; beta-amyloid; drugs; fibrils; impairments; marine sponges; mechanisms; microorganisms; neurotoxicity; oligomer; oxidative stress; sponge-associated fungus

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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