title: EGCG functions through estrogen receptor-mediated activation of ADAM10 in the promotion of non-amyloidogenic processing of APP.
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.
authors.affiliation: Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Tampa, FL 33613, USA. jfernan1@health.usf.edu
authors.forename: Jamie Winderbaum
authors.initials: JW
authors.lastname: Fernandez
authors.forename: Kavon
authors.initials: K
authors.lastname: Rezai-Zadeh
authors.forename: Demian
authors.initials: D
authors.lastname: Obregon
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000072197:ADAM10 Protein; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D045683:Furin / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016564:Amyloid beta-Protein Precursor; D047628:Estrogen Receptor alpha; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D002392:Catechin; C045651:epigallocatechin gallate; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053829:Amyloid Precursor Protein Secretases; D045683:Furin; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse