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EGCG functions through estrogen receptor‐mediated activation of ADAM10 in the promotion of non‐amyloidogenic processing of APP
Author(s) -
Fernandez Jamie Winderbaum,
Rezai-Zadeh Kavon,
Obregon Demian,
Tan Jun
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.09.022
Subject(s) - adam10 , furin , estrogen , amyloid precursor protein , estrogen receptor , chemistry , amyloid precursor protein secretase , endocrinology , medicine , cancer research , microbiology and biotechnology , alzheimer's disease , pharmacology , disintegrin , biochemistry , disease , biology , metalloproteinase , enzyme , breast cancer , cancer
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.