(-)-Epigallocatechin-3-gallate attenuates cognitive deterioration in Alzheimer's disease model mice by upregulating neprilysin expression
(-)-Epigallocatechin-3-gallate attenuates cognitive deterioration in Alzheimer's disease model mice by upregulating neprilysin expression
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(-)-表没食子儿茶素-3-没食子酸酯通过上调脑啡肽酶表达来减轻阿尔茨海默病模型小鼠的认知衰退
DOI：
10.1016/j.yexcr.2015.04.004
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发表时间：
2015-05-15
影响因子：
3.7
通讯作者：
Fang, Shuhuan
中科院分区：
文献类型：
--
作者：
Chang, Xiang;Rong, Cuiping;Fang, Shuhuan
表观遗传变化与学习和记忆有关，组蛋白脱乙酰酶 (HDAC) 抑制剂被认为是阿尔茨海默病 (AD) 的潜在治疗药物。我们之前报道过 (-)-表没食子儿茶素-3-没食子酸酯 (EGCG) 作为 HDAC 抑制剂。在这里，我们证明，EGCG 通过灌胃低剂量和高剂量 EGCG（分别为 5 和 15 mg/kg）60 天，可以在体外减少 β-淀粉样蛋白 (A beta) 积累，并挽救加速衰老小鼠 P8 (SAMP8) 的认知衰退。 AD 大脑中 Aβ 限速降解酶脑啡肽酶 (NEP) 的水平降低。我们发现 EGCG 诱导的 Aβ 积累减少与 NEP 表达升高之间存在关联。此外，NEP 沉默阻止了 EGCG 诱导的 Aβ 下调。我们的研究结果表明 EGCG 可能对治疗 AD 有效。 (C) 2015 Elsevier Inc. 保留所有权利。
Epigenetic changes are involved in learning and memory, and histone deacetylase (HDAC) inhibitors are considered potential therapeutic agents for Alzheimer's disease (AD). We previously reported that (-)-epigallocatechin-3-gallate (EGCG) acts as an HDAC inhibitor. Here, we demonstrate that EGCG reduced beta-amyloid (A beta) accumulation in vitro and rescued cognitive deterioration in senescence-accelerated mice P8 (SAMP8) via intragastric administration of low- and high-dose EGCG (5 and 15 mg/kg, respectively) for 60 days. The AD brain has decreased levels of the rate-limiting degradation enzyme of A beta, neprilysin (NEP). We found an association between EGCG-induced reduction in A beta accumulation and elevated NEP expression. Further, NEP silencing prevented the EGCG-induced A beta downregulation. Our findings suggest that EGCG might be effective for treating AD. (C) 2015 Elsevier Inc. All rights reserved.