Dehydroepiandrosterone (DHEA) increases production and release of Alzheimer's amyloid precursor protein.

Abstract:

:Dehydroepiandrosterone (DHEA), the major secretory product of the human adrenal cortex, significantly declines with advanced age. We have previously demonstrated that DHEA prevents the reduction in non-amyloidogenic APP processing, following prolonged stimulation of the muscarinic receptor, in PC12 cells that express the ml acetylcholine-receptor. The present study examined whether this effect may be mediated via modulation of APP metabolism. It was found that DHEA treatment increases the content of membrane-associated APP holoprotein by 24%, and the accumulation of secreted APP in the medium by 63%. No increase in viable cell number nor in nonspecific protein production was observed in DHEA-treated cells. Thus, DHEA seems to increase specifically both APP synthesis and secretion. We propose that the age-associated decline in DHEA levels may be related to the pathological APP metabolism observed in Alzheimer's disease.

journal_name

Life Sci

journal_title

Life sciences

authors

Danenberg HD,Haring R,Fisher A,Pittel Z,Gurwitz D,Heldman E

doi

10.1016/0024-3205(96)00496-1

subject

Has Abstract

pub_date

1996-01-01 00:00:00

pages

1651-7

issue

19

eissn

0024-3205

issn

1879-0631

pii

0024320596004961

journal_volume

59

pub_type

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