Peroxisome-proliferator-activated Receptor Gamma Induces a Clearance Mechanism for the Amyloid-beta Peptide

Overview

Journal J Neurosci

Specialty Neurology

Date 2004 Dec 3

PMID 15574741

Citations 66

Authors

Ira Espuny Camacho

Lutgarde Serneels

Kurt Spittaels

Pascal Merchiers

Diana Dominguez

Bart De Strooper

Affiliations

Soon will be listed here.

Abstract

We investigated whether peroxisome proliferator-activated receptor gamma (PPARgamma) could be involved in the modulation of the amyloid cascade causing Alzheimer's disease. Inducing expression or activating PPARgamma using synthetic agonists of the thiazolinedione family results in a dramatic decrease in the levels of the amyloid-beta (Abeta) peptide in the conditioned medium of neuronal and non-neuronal cells. PPARgamma does not affect expression or activity of any of the secretases involved in the generation of the Abeta peptide but induces a fast, cell-bound clearing mechanism responsible for the removal of the Abeta peptide from the medium. Although PPARgamma expression is generally low in the CNS, induction of PPARgamma expression during inflammation could be beneficial for inducing Abeta clearance. We confirm that the Abeta clearance mechanism can indeed be induced by PPARgamma activation in primary murine-mixed glia and cortical neuronal cultures. Our results suggest that PPARgamma-controlled mechanisms should be explored further as potential drug targets for Alzheimer's disease treatment.

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