Inhibition of ACAT, overexpression of cholesterol transporter gene, and protection of amyloid β oligomers-induced neuronal cell death by tricyclic pyrone molecules

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dc.contributor.author Pokhrel, Laxman
dc.contributor.author Maezawa, Izumi
dc.contributor.author Nguyen, Thi D.T.
dc.contributor.author Chang, Kyeong-Ok
dc.contributor.author Jin, Lee-Way
dc.contributor.author Hua, Duy H.
dc.date.accessioned 2012-12-11T21:15:45Z
dc.date.available 2012-12-11T21:15:45Z
dc.date.issued 2012-12-11
dc.identifier.uri http://hdl.handle.net/2097/15172
dc.description.abstract Alzheimer’s disease (AD) is the most common cause of dementia in the elderly. A major effort in AD therapeutic development has targeted Aβ and downstream events. We have taken a rational design approach and synthesized a small library of tricyclic pyrone compounds based on CP2. Their protective action in MC65 cells and the inhibition of acyl‐CoA:cholesterol acyltransferase along with the upregulation of cholesterol transporter gene were investigated. Five most active compounds exhibited potencies in the nanomolar to low micromolar ranges. The multiple effects of the compounds on Aβ and cellular cholesterol pathways could be potential mechanisms underlying the protective effects in vivo. en_US
dc.language.iso en_US en_US
dc.relation.uri http://pubs.acs.org/doi/abs/10.1021/jm3012189 en_US
dc.rights Permission to archive granted by the editors of the Journal of Medicinal Chemistry, November 29, 2012. This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in Journal of Medicinal Chemistry, copyright © American Chemical Society after peer review. To access the final edited and published work see http://pubs.acs.org/doi/pdfplus/10.1021/jm3012189 en_US
dc.subject Alzheimer’s disease en_US
dc.subject en_US
dc.subject Tricyclic pyrone molecules en_US
dc.subject Cholesterol transporter gene en_US
dc.subject Acyl‐CoA:cholesterol acyltransferase en_US
dc.title Inhibition of ACAT, overexpression of cholesterol transporter gene, and protection of amyloid β oligomers-induced neuronal cell death by tricyclic pyrone molecules en_US
dc.title.alternative Inhibition of Acyl-CoA: Cholesterol acyltransferase (ACAT), overexpression of cholesterol transporter gene, and protection of amyloid β (Aβ) oligomers-induced neuronal cell death by tricyclic pyrone molecules en_US
dc.type Article (author version) en_US
dc.date.published 2012 en_US
dc.citation.doi doi:10.1021/jm3012189 en_US
dc.citation.epage 8973 en_US
dc.citation.issue 20 en_US
dc.citation.jtitle Journal of Medicinal Chemistry en_US
dc.citation.spage 8969 en_US
dc.citation.volume 55 en_US
dc.contributor.authoreid duy en_US


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