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Sci Signal:上海中医药大学陈瑜研究组等发表信号转导新文章

摘要 : 2016年7月26日,国际顶尖学术期刊《Science》旗下《Science Signaling》杂志上在线发表了上海中医药大学陈瑜教授和凯斯西储大学Krzysztof Palczewski教授合作的一篇研究论文,研究证实协同作用的G蛋白偶联受体激动剂与拮抗剂可以阻止光感受器细胞退化。

 2016年7月26日,国际顶尖学术期刊《Science》旗下《Science Signaling》杂志上在线发表了上海中医药大学陈瑜教授和凯斯西储大学Krzysztof Palczewski教授合作的一篇研究论文,研究证实协同作用的G蛋白偶联受体激动剂与拮抗剂可以阻止光感受器细胞退化。





Synergistically acting agonists and antagonists of G protein–coupled receptors prevent photoreceptor cell degeneration


Photoreceptor cell degeneration leads to visual impairment and blindness in several types of retinal disease. However, the discovery of safe and effective therapeutic strategies conferring photoreceptor cell protection remains challenging. Targeting distinct cellular pathways with low doses of different drugs that produce a functionally synergistic effect could provide a strategy for preventing or treating retinal dystrophies. We took a systems pharmacology approach to identify potential combination therapies using a mouse model of light-induced retinal degeneration. We showed that a combination of U.S. Food and Drug Administration–approved drugs that act on different G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors (GPCRs) exhibited synergistic activity that protected retinas from light-induced degeneration even when each drug was administered at a low dose. In functional assays, the combined effects of these drugs were stimulation of Gi/o signaling by activating the dopamine receptors D2R and D4R, as well as inhibition of Gs and Gq signaling by antagonizing D1R and the α1A-adrenergic receptor ADRA1A, respectively. Moreover, transcriptome analyses demonstrated that such combined GPCR-targeted treatments preserved patterns of retinal gene expression that were more similar to those of the normal retina than did higher-dose monotherapy. Our study thus supports a systems pharmacology approach to identify treatments for retinopathies, an approach that could extend to other complex disorders.

来源: Science Signaling 浏览次数:0


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