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淋巴细胞G蛋白偶联受体激酶2在阿尔茨海默病患者中上调。

Lymphocyte G-protein-coupled receptor kinase-2 is upregulated in patients with Alzheimer's disease.

作者信息

Leosco Dario, Fortunato Francesca, Rengo Giuseppe, Iaccarino Guido, Sanzari Emma, Golino Luca, Zincarelli Carmela, Canonico Vincenzo, Marchese Massimo, Koch Walter J, Rengo Franco

机构信息

Dipartimento di Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, Università Federico II, Via Pansini 5, Edificio 2, 80131 Naples, Italy.

出版信息

Neurosci Lett. 2007 Mar 30;415(3):279-82. doi: 10.1016/j.neulet.2007.01.034. Epub 2007 Jan 19.

Abstract

Alterations in signal transduction pathway of G-protein-coupled receptors (GPCRs) have been found in the cerebrocortex and in the peripheral cultured tissues of patients with Alzheimer's disease (AD). The G-protein-coupled receptor kinase-2 (GRK2) plays an important role in regulating the GPCRs signaling: its increased expression is associated with receptor desensitization. The aim of this study was to explore GRK2 levels in peripheral lymphocytes of AD patients and to establish a correlation between lymphocyte protein concentrations and the degree of cognitive impairment. GRK2 mRNA and protein expression were evaluated in the lymphocytes of AD patients with mild or moderate/severe cognitive impairment and in age-matched healthy subjects. Both GRK2 mRNA and protein expression were higher in AD patients lymphocytes compared to controls. Furthermore, lymphocyte GRK2 levels were significantly correlated to the degree of cognitive decline. Our preliminary data suggest that GRK2 is involved in GPCRs coupling dysfunction observed in AD patients. Further studies are needed in order to verify whether the lymphocyte GRK2 might be utilized as a novel biomarker in AD diagnosis and clinical monitoring.

摘要

在阿尔茨海默病(AD)患者的大脑皮质及外周培养组织中,已发现G蛋白偶联受体(GPCRs)信号转导通路存在改变。G蛋白偶联受体激酶2(GRK2)在调节GPCRs信号传导中起重要作用:其表达增加与受体脱敏相关。本研究的目的是探讨AD患者外周淋巴细胞中GRK2水平,并建立淋巴细胞蛋白浓度与认知障碍程度之间的相关性。对轻度或中度/重度认知障碍的AD患者及年龄匹配的健康受试者的淋巴细胞进行GRK2 mRNA和蛋白表达评估。与对照组相比,AD患者淋巴细胞中的GRK2 mRNA和蛋白表达均更高。此外,淋巴细胞GRK2水平与认知衰退程度显著相关。我们的初步数据表明,GRK2参与了AD患者中观察到的GPCRs偶联功能障碍。需要进一步研究以验证淋巴细胞GRK2是否可作为AD诊断和临床监测的新型生物标志物。

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