G蛋白信号调节蛋白作为中枢神经系统药物新靶点研究进展

Research progress in regulators of G-protein signaling as new central nervous system drug targets

G蛋白偶联受体(G-prote in-coup led receptors,GPCR)是许多治疗药物的作用靶点。G蛋白信号调节蛋白(regu latorof G-prote in signaling,RGS)属一类新发现的蛋白家族,它们在GPCR信号传导中起重要作用。一般来说RGS可加速G蛋白失活进而终止GPCR信号传导,但也有些RGS同时具有效应分子和信号传递功能。兼具GPCR激动和RGS抑制功能的药物将大大增强信号传导,同时还能增加激动剂的区域特异性。由于RGS的多样性,组织分布特异性以及较强的调节活性,RGS很可能成为寻找新型中枢神经系统疾病治疗药物的新靶点。

G-protein-coupled receptors （GPCRs） are major targets for drug discovery. The regulator of G- protein signaling （RGS） proteins is a recently identified protein family, which strongly modulates the activity of G proteins. RGS proteins accelerate the deactivation of G proteins to reduce （;PCR signaling; however, some also have an effector function and transmit signals. Combining GPCR agonists with RGS inhibitorsshould potentiate responses and markedly increase the regional specificity of agonist. In the central nervous system, RGS proteins have unique tissue distributions and are strongly regulated by signal transduction events. Thus the diversity of RGS makes them attractive targets for pharmacotherapy of neurological disorders.