EGCG 通过雌激素受体介导的 ADAM10 激活促进 APP 的非淀粉样蛋白生成过程。
EGCG functions through estrogen receptor-mediated activation of ADAM10 in the promotion of non-amyloidogenic processing of APP.
机构信息
Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Tampa, FL 33613, USA.
出版信息
FEBS Lett. 2010 Oct 8;584(19):4259-67. doi: 10.1016/j.febslet.2010.09.022. Epub 2010 Sep 17.
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.
摘要
绝经后雌激素耗竭与阿尔茨海默病（AD）的发病风险增加有关。我们之前研究了（-）-表没食子儿茶素没食子酸酯（EGCG）对 AD 小鼠的有益作用，发现通过α-分泌酶 a 型整合素金属蛋白酶域 10（ADAM10）增加了淀粉样前体蛋白（APP）的非淀粉样生成处理。我们在这项研究中的结果表明，EGCG 通过雌激素受体-α（ERα）/磷酸肌醇 3-激酶/Ak 转化依赖性机制促进 ADAM10 的成熟，从而介导 APP 的非淀粉样生成处理的增强，而不依赖于弗林介导的 ADAM10 激活。这些数据支持中枢选择性 ER 调节可能是 AD 的治疗靶点的观点，并支持将 EGCG 作为一种耐受良好的雌激素替代疗法，用于预防和治疗这种疾病。
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