Inhibition of glycogen synthase kinase-3 suppresses the onset of symptoms and disease progression of G93A-SOD1 mouse model of ALS
Inhibition of glycogen synthase kinase-3 suppresses the onset of symptoms and disease progression of G93A-SOD1 mouse model of ALS
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DOI：
10.1016/j.expneurol.2007.03.004
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发表时间：
2007-06-01
影响因子：
5.3
通讯作者：
Kim, Seung H.
中科院分区：
文献类型：
--
作者：
Koh, Seong-Ho;Kim, Youngchul;Kim, Seung H.
糖原合成酶激酶（GSK）-3最近被牵连在神经退行性疾病的发病机制。尽管GSK-3抑制剂对阿尔茨海默病的神经保护作用已得到证实，但其对肌萎缩侧索硬化症（ALS）的作用尚未得到很好的定义。进行本研究以评估GSK-3抑制在ALS的G93 A-SODI小鼠模型中的作用。G93 A-SODI小鼠组在60日龄后每周5天腹膜内用不同浓度的GSK-3抑制剂VIII（一种穿过BBB的特异性GSK-3抑制剂）处理。GSK-3抑制剂VIII治疗显著延迟症状发作并延长动物寿命，并以浓度依赖性方式抑制GSK-3的活性。此外，这种治疗保留了存活信号并减弱了死亡和炎症信号。这些数据表明GSK-3在ALS的致病机制中起重要作用，并且GSK-3的抑制可能是ALS的潜在治疗候选物。(c)2007年爱思唯尔公司All rights reserved.
Glycogen synthase kinase (GSK)-3 has recently been implicated in the pathogenesis of neurodegenerative diseases. Although the neuroprotective effects of GSK-3 inhibitors in Alzheimer's disease have been established, their effects on amyotrophic lateral sclerosis (ALS) have not been well defined. This study was undertaken to evaluate the effects of GSK-3 inhibition in the G93A-SODI mouse model of ALS. Groups of G93A-SODI mice were treated with varying concentrations of GSK-3 inhibitor VIII, a specific GSK-3 inhibitor that crosses the BBB, intraperitoneally 5 days a week after 60 days of age. The GSK-3 inhibitor VIII treatment significantly delayed the onset of symptoms and prolonged the life span of the animals, and inhibited the activity of GSK-3 in a concentration-dependent manner. Furthermore, this treatment preserved survival signals and attenuated death and inflammatory signals. These data suggest that GSK-3 plays an important role in the pathogenic mechanisms of ALS and that inhibition of GSK-3 could be a potential therapeutic candidate for ALS. (c) 2007 Elsevier Inc. All rights reserved.