First Author | Fernandez JW | Year | 2010 |
Journal | FEBS Lett | Volume | 584 |
Issue | 19 | Pages | 4259-67 |
PubMed ID | 20849853 | Mgi Jnum | J:164658 |
Mgi Id | MGI:4834937 | Doi | 10.1016/j.febslet.2010.09.022 |
Citation | Fernandez JW, et al. (2010) EGCG functions through estrogen receptor-mediated activation of ADAM10 in the promotion of non-amyloidogenic processing of APP. FEBS Lett 584(19):4259-67 |
abstractText | 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 (ERalpha)/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. |