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Inhibition of Acyl-CoA: cholesterol acyltransferase (ACAT), overexpression of cholesterol transporter gene, and protection of amyloid ? (A?) oligomers-induced neuronal cell death by tricyclic pyrone molecules.

ABSTRACT: A major effort in Alzheimer's disease therapeutic development has targeted A? and downstream events. We have synthesized a small library of tricyclic pyrone compounds. Their protective action in MC65 cells and inhibition of ACAT along with the upregulation of cholesterol transporter gene were investigated. Five active compounds exhibited potencies in the nanomolar ranges. The multiple effects of the compounds on A? and cellular cholesterol pathways could be potential mechanisms underlying the protective effects in vivo.

SUBMITTER: Pokhrel L

PROVIDER: S-EPMC3486708 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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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.

Pokhrel Laxman L Maezawa Izumi I Nguyen Thi D T TD Chang Kyeong-Ok KO Jin Lee-Way LW Hua Duy H DH

Journal of medicinal chemistry 20121005 20

A major effort in Alzheimer's disease therapeutic development has targeted Aβ and downstream events. We have synthesized a small library of tricyclic pyrone compounds. Their protective action in MC65 cells and inhibition of ACAT along with the upregulation of cholesterol transporter gene were investigated. Five active compounds exhibited potencies in the nanomolar ranges. The multiple effects of the compounds on Aβ and cellular cholesterol pathways could be potential mechanisms underlying the pr ...[more]

PMID: 23025824

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