EGCG functions through estrogen receptor‐mediated activation of ADAM10 in the promotion of non‐amyloidogenic processing of APP
Open Access
- 16 September 2010
- journal article
- research article
- Published by Wiley in FEBS Letters
- Vol. 584 (19), 4259-4267
- https://doi.org/10.1016/j.febslet.2010.09.022
Abstract
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 α-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-α (ERα)/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.Keywords
Funding Information
- NCAAM (R43AT004871)
- NIA (R43AG033417)
- Veterans Affairs MERIT
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