Indirubin-3′-monoxime rescues spatial memory deficits and attenuates β-amyloid-associated neuropathology in a mouse model of Alzheimer's disease
Indirubin-3′-monoxime rescues spatial memory deficits and attenuates β-amyloid-associated neuropathology in a mouse model of Alzheimer's disease
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DOI：
10.1016/j.nbd.2010.03.022
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发表时间：
2010-08-01
影响因子：
6.1
通讯作者：
Fan, Guo-Huang
中科院分区：
文献类型：
--
作者：
Ding, Yun;Qiao, Aimin;Fan, Guo-Huang
靛玉红及其衍生物已被证明对细胞周期蛋白依赖性蛋白激酶 5 和糖原合酶激酶 313 具有有效的抑制作用，这两种蛋白激酶参与 tau 异常过度磷酸化和淀粉样蛋白前体蛋白加工/β-淀粉样蛋白 (Aβ) 的产生。在这里，我们发现，用靛玉红-3'-单肟（IMX；20 mg/kg：每周 3 次）对 APP 和早老素 1 (PS1) 转基因小鼠（一种稳健的阿尔茨海默病 (AD) 小鼠模型）进行全身治疗，为期短短 2 个月，可显着减轻空间记忆缺陷。与此同时，一些 AD 样表型显着减少，包括 Aβ 沉积、tau 蛋白过度磷酸化、Aβ 斑块周围激活的小胶质细胞和星形胶质细胞的积累，以及突触素免疫反应性的丧失。这些发现表明 IMX 是对抗 AD 的潜在治疗剂。 (C) 2010 Elsevier Inc. 保留所有权利。
Indirubin and its derivatives have been shown to possess potent inhibitory effects on cyclin-dependent protein kinase 5 and glycogen synthase kinase 313, two protein kinases involved in abnormal hyperphosphorylation of tau and amyloid precursor protein processing/beta-amyloid (A beta) production. Here, we showed that systemic treatment of APP and presenilin 1 (PS1) transgenic mice, a robust Alzheimer's disease (AD) mouse model, with indirubin-3'-monoxime (IMX; 20 mg/kg: 3 times weekly), for as little as 2 months, significantly attenuated spatial memory deficits. This was accompanied by a marked decrease in several AD-like phenotypes, including A beta deposition, tau hyperphosphorylation, accumulation of activated microglia and astrocytes around A beta plaques, and loss of synaptophysin immunoreactivity. These findings suggest that IMX is a potential therapeutic agent to combat AD. (C) 2010 Elsevier Inc. All rights reserved.