Alpha1-chimaerin, a Rac1 GTPase-activating protein, is expressed at reduced mRNA levels in the brain of Alzheimer's disease patients.

Alpha1-chimaerin, a Rac1 GTPase-activating protein, is expressed at reduced mRNA levels in the brain of Alzheimer's disease patients.
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DOI:
10.1016/j.neulet.2015.02.013
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发表时间:
2015-03-30
影响因子:
2.5
通讯作者:
Tooyama I
Tooyama I
中科院分区:
医学4区
文献类型:
--
作者:
Kato T;Konishi Y;Shimohama S;Beach TG;Akatsu H;Tooyama I

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α1嵌合体是Rho小分子GTPase家族成员rac1的GTP酶激活蛋白(GAP),它的作用导致rac1失活。α1活性在阿尔茨海默病中上调,但对RAC1-嵌合体的作用知之甚少。在这项研究中,我们研究了α1-嵌合体在阿尔茨海默病患者和对照组死后人脑中的表达和定位。原位杂交研究表明,α1-嵌合体在对照组和阿尔茨海默病患者的颞叶新皮质和海马神经元中均有表达,阿尔茨海默病患者的信号强度显著降低。实时定量聚合酶链式反应分析证实,阿尔茨海默病患者颞叶皮质中α1-嵌合体基因的表达显著减少。相反,α-2-嵌合体基因表达水平在两组间无显著差异。目前的研究表明,在阿尔茨海默病患者的大脑中,α1-嵌合体的表达减少,这表明在疾病过程中,Rac1的活性上调起到了作用。
Alpha1-chimaerin is a GTPase-activating protein (GAP) for Rac1, a member of the Rho small GTPase family, whose action leads to the inactivation of Rac1. Rac1 activity is upregulated in Alzheimer's disease, but little is known about the role of α1-chimaerin. In this study, we investigated the expression and localization of α1-chimaerin mRNA in postmortem human brains from patients with Alzheimer's disease and control subjects. In situ hybridization studies demonstrated that α1-chimaerin was expressed by neurons in the neo-cortex of the temporal lobe and the hippocampus of both controls and Alzheimer's disease cases, with the signal intensity dramatically decreased in patients with Alzheimer's disease. Real-time PCR analysis confirmed a significant reduction of α1-chimaerin mRNA expression in the temporal cortex of Alzheimer's disease cases. In contrast, α2-chimaerin mRNA levels showed no significant difference between the groups. The present study showed reduced α1-chimaerin expression in the brain of Alzheimer's disease cases, suggesting a role in the upregulation of Rac1 activity during the disease process.
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