打开APP

J Neurosci:糖尿病药物或可提高阿尔茨海默氏症患者记忆力

  1. 罗格列酮
  2. 阿尔茨海默氏症

来源:生物谷 2013-04-27 15:20

近日,一项最新研究证实FDA批准的最初用于治疗糖尿病患者的药物可能会改善阿尔茨海默氏症患者的认知能力。 利用阿尔茨海默氏症遗传工程小鼠,得克萨斯医学科大学研究人员发现,治疗抗胰岛素抵抗的药物罗格列酮能增强小鼠的学习和记忆能力。 在阿尔茨海默氏症患者大脑以及相应的患阿尔茨海默氏症的小鼠体内,细胞外信号调节激酶(ERK)变得异常活跃。这种过度活动导致神经元之间的突触传递不当,干扰了学习和记忆能力。

近日,一项最新研究证实FDA批准的最初用于治疗糖尿病患者的药物可能会改善阿尔茨海默氏症患者的认知能力。

利用阿尔茨海默氏症遗传工程小鼠,得克萨斯医学科大学研究人员发现,治疗抗胰岛素抵抗的药物罗格列酮能增强小鼠的学习和记忆能力。

在阿尔茨海默氏症患者大脑以及相应的患阿尔茨海默氏症的小鼠体内,细胞外信号调节激酶(ERK)变得异常活跃。这种过度活动导致神经元之间的突触传递不当,干扰了学习和记忆能力。而罗格列酮能将ERK恢复到原来正常水平,其机制为通过激活过氧化物酶增殖体激活受体PPARγ信号途径。

这项最新研究成果发表在Journal of Neuroscience杂志上。研究团队预测试FDA批准的几个改善胰岛素抵抗的药物对阿尔茨海默氏症患者记忆的影响。

几年前,副教授Kelly Dineley发现阿尔茨海默氏症小鼠模型ERK功能障碍。但将该蛋白质,与记忆功能联系起来还是首次提出。

现在,研究小组正在世界各地开始临床试验,以探讨胰岛素抵抗治疗药物对早期老年痴呆症疾病的价值。(生物谷:Bioon.com)

Cognitive Enhancement with Rosiglitazone Links the Hippocampal PPARγ and ERK MAPK Signaling Pathways

Larry A. Denner, Jennifer Rodriguez-Rivera, et al.

We previously reported that the peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (RSG) improved hippocampus-dependent cognition in the Alzheimer's disease (AD) mouse model, Tg2576. RSG had no effect on wild-type littermate cognitive performance. Since extracellular signal-regulated protein kinase mitogen-activated protein kinase (ERK MAPK) is required for many forms of learning and memory that are affected in AD, and since both PPARγ and ERK MAPK are key mediators of insulin signaling, the current study tested the hypothesis that RSG-mediated cognitive improvement induces a hippocampal PPARγ pattern of gene and protein expression that converges with the ERK MAPK signaling axis in Tg2576 AD mice. In the hippocampal PPARγ transcriptome, we found significant overlap between peroxisome proliferator response element-containing PPARγ target genes and ERK-regulated, cAMP response element-containing target genes. Within the Tg2576 dentate gyrus proteome, RSG induced proteins with structural, energy, biosynthesis and plasticity functions. Several of these proteins are known to be important for cognitive function and are also regulated by ERK MAPK. In addition, we found the RSG-mediated augmentation of PPARγ and ERK2 activity during Tg2576 cognitive enhancement was reversed when hippocampal PPARγ was pharmacologically antagonized, revealing a coordinate relationship between PPARγ transcriptional competency and phosphorylated ERK that is reciprocally affected in response to chronic activation, compared with acute inhibition, of PPARγ. We conclude that the hippocampal transcriptome and proteome induced by cognitive enhancement with RSG harnesses a dysregulated ERK MAPK signal transduction pathway to overcome AD-like cognitive deficits in Tg2576 mice. Thus, PPARγ represents a signaling system that is not crucial for normal cognition yet can intercede to restore neural networks compromised by AD.

版权声明 本网站所有注明“来源:生物谷”或“来源:bioon”的文字、图片和音视频资料,版权均属于生物谷网站所有。非经授权,任何媒体、网站或个人不得转载,否则将追究法律责任。取得书面授权转载时,须注明“来源:生物谷”。其它来源的文章系转载文章,本网所有转载文章系出于传递更多信息之目的,转载内容不代表本站立场。不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。

87%用户都在用生物谷APP 随时阅读、评论、分享交流 请扫描二维码下载->