Dehydroepiandrosterone (DHEA) increases production and release of Alzheimer's amyloid precursor protein
Autor: | Abraham Fisher, Rachel Haring, Eliahu Heldman, H.D. Danenberg, David Gurwitz, Z. Pittel |
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Rok vydání: | 1996 |
Předmět: |
medicine.medical_specialty
Indoles Dehydroepiandrosterone Cell Count PC12 Cells General Biochemistry Genetics and Molecular Biology Maleimides Amyloid beta-Protein Precursor Alzheimer Disease Internal medicine mental disorders Muscarinic acetylcholine receptor polycyclic compounds medicine Amyloid precursor protein Protein biosynthesis Animals Humans Secretion Enzyme Inhibitors General Pharmacology Toxicology and Pharmaceutics Protein Kinase C Dose-Response Relationship Drug biology Chemistry Adrenal cortex General Medicine Rats Dose–response relationship medicine.anatomical_structure Endocrinology Protein Biosynthesis biology.protein Signal transduction hormones hormone substitutes and hormone antagonists Signal Transduction |
Zdroj: | Life Sciences. 59:1651-1657 |
ISSN: | 0024-3205 |
Popis: | 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. |
Databáze: | OpenAIRE |
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