多巴胺和环磷酸腺苷调节的磷酸蛋白在神经元信号传递及整合中的地位(英文)

Role of dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein in neuronal signal transmission and integration

目的:阐明多巴胺和环磷酸腺苷调节的磷酸蛋白在神经元信号传递及整合中的中心作用,为神经系统疾病的治疗和功能恢复提供基础研究的假说理论。资料来源:应用计算机检索Medline数据库1980-01/2004-12的相关文献,检索词为“DARPP-32”和“role”,限定文章语言种类为英文。同时计算机检索中国期刊全文数据库和万方数据库1980-01/2004-12的相关文献,检索词为“磷酸蛋白,作用”,限定文章种类为中文。资料选择:对所选择的98篇资料进行初审,选取与目的有直接关系的文章,纳入标准:①随机对照试验。②专著中的章节。排除重复性研究和Meta分析。资料提炼:共收集到29篇关于多巴胺和环磷酸腺苷调节的磷酸蛋白的研究原著、综述和书籍文献。根据其相应的结果和讨论进行资料概括、综合和提炼。资料综合:①ARPP-32蛋白是脑内新纹状体等重要核团的神经元内存在的一种具有多方面信息调节与整合作用的蛋白质。②多巴胺、谷氨酸等神经递质与相应受体结合后,使多巴胺和环磷酸腺苷调节的磷酸蛋白的34-苏氨酸等磷酸化状态发生改变,继之影响磷酸酯酶I、磷酸酯酶2B等重要磷酸酯酶的活性,从而使神经元内从各种途径获取的信息得以整合,神经元的生理功能及其控制的行为发生改变。③多巴胺和环磷酸腺苷调节的磷酸蛋白的功能与多种神经递质及其受体密切相关。④多巴胺和环磷酸腺苷调节的磷酸蛋白的功能可用基因敲除技术进行探究。结论:多巴胺和环磷酸腺苷调节的磷酸蛋白在复杂的神经元信号传递和整合过程中居于中心位置。对多巴胺和环磷酸腺苷调节的磷酸蛋白的研究也将为神经系统疾病如帕金森症、亨廷顿症、精神分裂症及吸毒成瘾等治疗和康复提供有效的依据和手段。

OBJECTIVE： To elucidate the central role of dopamine-and cyclic adenosine 3＇,5＇-monophosphate-regulated phosphoprotein （DARPP 32） in neuronal signal transmission and integration to provide a theoretical basis for study of the clinical treatment and functional rehabilitation of neurological diseases. DATA SOURCES： A cmnputer-based search was conducted for related literatures published between January. 1980 anti December 2004 indexed in Mediine Database, using the key words of “DARPP-32” and “role”, with the language of the articles limited to Etlglish. A similar search was also conducted for Chinese articles indexed in Chinese Academic Journal Full-text Database and Wanfang Database, using the equivalent Chinese terms for the same key words. STUDY SELECTION： A preliminary selection of the 98 retrieved articles was carried out to identify randomized controlled experiments or trials and relevant chapters in monographs for inclusion, with repetitive studies and Meta-analysis excluded. DATA EXTRACTION： Totally 29 original articles, reviews and monographs pertaining to the study of DARPP-32 were collected. Summarization, synthesis and abstraction of the articles was carried out according to the results and discussions in the articles. DATA SYNTHESIS： DARPP-32 is expressed in the neurons in the neostriatum and other nuclei, performing multiple roles in signal regulation and integration. After binding to corresponding receptors, dopamine, glutamate or other neurotransmitters cause phosphorylation or dephosphorylation of DARPP-32 at 34-Thr or other three sites to affect the activities of such important phospholipases as phospholipase 1 and 2B, so that all the signals from various pathways can be integrated and the neuronal functions and the behaviors governed by these neurons altered. The functions of DARPP- 32 are related to many neurotransmitters and their receptors and can be explored using gene knockout technique. CONCLUSION： DARPP-32 plays a central role in the complex signal transmission and integration processes of neurons. The research of DARPP- 32 may provide evidence and effective means for the therapy of neurologi- cal diseases such as Parkinson disease, Huntington disease, schizophrenia and drug addiction.