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EGCG functions through estrogen receptor-mediated activation of ADAM10 in the promotion of non-amyloidogenic processing of APP |
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| Authors: | Jamie Winderbaum Fernandez Kavon Rezai-Zadeh Jun Tan |
| Affiliation: | a Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Tampa, FL 33613, USA b Department of Psychiatry and Neurosciences, College of Medicine, University of South Florida, Tampa, FL 33613, USA c Department of Biomedical Sciences, Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA |
| 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: | Alzheimer&rsquo s disease Estrogen Amyloid precursor protein Phosphoinositide 3-kinase Furin Epigallocatechin gallate A disintegrin and metalloprotease domain 10 |
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