PMID: 8597471Dec 29, 1995Paper

Dehydroepiandrosterone augments M1-muscarinic receptor-stimulated amyloid precursor protein secretion in desensitized PC12M1 cells

Annals of the New York Academy of Sciences
H D DanenbergA Fisher

Abstract

Epidemiologic studies suggest that the age-related decline in dehydroepiandrosterone (DHEA) levels may be associated with Alzheimer's disease (AD). Cholinergic markers also decline with age, and are associated with AD pathology. Activation of m1AChR-transfected PC12 cells (PC12M1) with cholinergic agonists results in secretion of Alzheimer's beta-amyloid precursor protein (APP) which in turn reduces beta-amyloid production. This study examined whether DHEA affects APP processing in m1AChR-transfected PC12 cells. DHEA treatment did not significantly alter basal or m1AChR-stimulated APP secretion. However, DHEA (0.1 microM) significantly diminished the desensitization of APP secretion in cells exposed to carbachol for 24 h. The effect of DHEA on APP processing is probably not related to up-regulation of m1AChR or increased m1AChR-activated phosphoinositide hydrolysis since these parameters did not change following DHEA treatment. These findings imply a possible involvement of DHEA in APP processing. Thus, the age-associated decline in DHEA levels may contribute to decreased APP secretion and a consecutive increase in beta-amyloid deposition, which in turn may play a role in the development of AD.

Citations

Oct 16, 1999·The Journal of Clinical Endocrinology and Metabolism·A J Lerner
Dec 6, 2003·Alzheimer Disease and Associated Disorders·Sam GandyJoseph Buxbaum
Nov 5, 2002·The Journal of Clinical Endocrinology and Metabolism·Sébastien Weill-EngererYvette Akwa
Feb 2, 2002·Free Radical Biology & Medicine·J A JosephJ Strain
Aug 26, 1999·Trends in Endocrinology and Metabolism : TEM·S Gandy
Jul 19, 2000·Biochimica Et Biophysica Acta·S Gandy, S Petanceska

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