|Title||5-Hydroxycyclopenicillone Inhibits beta-Amyloid Oligomerization and Produces Anti-beta-Amyloid Neuroprotective Effects In Vitro|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Zhao 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.|
|Type of Article||Article|
|Keywords||5-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.