Journal
FEBS LETTERS
Volume 584, Issue 19, Pages 4259-4267Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2010.09.022
Keywords
Alzheimer's disease; Estrogen; Amyloid precursor protein; Phosphoinositide 3-kinase; Furin; Epigallocatechin gallate; A disintegrin and metalloprotease domain 10
Funding
- NCAAM [R43AT004871]
- NIA [R43AG033417]
- Veterans Affairs
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Estrogen depletion following menopause has been correlated with an increased risk of developing Alzheimer's disease (AD). We previously explored the beneficial effect of (-)-epigallocatechin-3-gallate (EGCG) on AD mice and found increased non-amyloidogenic processing of amyloid precursor protein (APP) through the alpha-secretase a disintegrin and metallopeptidase domain 10 (ADAM10). Our results in this study suggest that EGCG-mediated enhancement of non-amyloidogenic processing of APP is mediated by the maturation of ADAM10 via an estrogen receptor-alpha (ER alpha)/phosphoinositide 3-kinase/Ak-transforming dependent mechanism, independent of furin-mediated ADAM10 activation. These data support prior assertions that central selective ER modulation could be a therapeutic target for AD and support the use of EGCG as a well-tolerated alternative to estrogen therapy in the prophylaxis and treatment of this disease. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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