Activation of 5-HT4 receptors inhibits secretion of β-amyloid peptides and increases neuronal survival
Activation of 5-HT4 receptors inhibits secretion of β-amyloid peptides and increases neuronal survival
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DOI：
10.1016/j.expneurol.2006.07.021
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发表时间：
2007-01-01
影响因子：
5.3
通讯作者：
Hu, Yun
中科院分区：
文献类型：
--
作者：
Cho, Seongeun;Hu, Yun
5-HT4受体的激活被证明可以改善临床前认知模型的记忆过程，这表明5-HT4激动剂可能用于阿尔茨海默病(AD)的对症治疗。最近的研究表明，5-HT4激动剂还增加了非淀粉样变性可溶性淀粉样前体蛋白-α(Sappα)的分泌。在本研究中，我们证明了选择性5-HT4部分激动剂RS67333可以抑制表达人APP(K670N/M671L)的Tg2576转基因小鼠大脑皮质原代培养中β-淀粉样肽(Aβ)的产生。此外，RS67333以剂量依赖的方式选择性地增加转基因神经元的存活率，这一作用可被5-HT4拮抗剂抑制。这些和以前的数据共同表明，5-HT4受体可能是AD的有效治疗靶点，既能改善症状，又能提供神经保护。(C)2006 Elsevier Inc.保留所有权利。
Activation of 5-HT4 receptors has been shown to improve memory processes in preclinical cognition models, suggesting potential utility of 5-HT4 agonists for the symptomatic treatment of Alzheimer's disease (AD). Recent studies have shown that 5-HT4 agonists also increase the secretion of the non-amyloidogenic soluble amyloid precursor protein-alpha (sAPP alpha). In the present study, we demonstrated that a selective 5-HT4 partial agonist, RS67333, inhibited the generation of beta-amyloid peptide (A beta) in primary cortical cultures of Tg2576 transgenic mice expressing human APP(K670N/M671L). Furthermore, treatments with RS67333 selectively increased the survival of transgenic neurons in a dose-dependent manner, which was inhibited by 5-HT4 antagonists. These and previous data collectively suggest that the 5-HT4 receptor may be an effective therapeutic target for AD, providing both symptomatic improvements and neuroprotection. (c) 2006 Elsevier Inc. All rights reserved.