与尼古丁成瘾相关的神经系统信号通路分析

项目名称： 与尼古丁成瘾相关的神经系统信号通路分析

项目编号： No.31271411

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 王举

作者单位： 天津医科大学

项目金额： 60万元

中文摘要： 研究尼古丁成瘾的分子机理对于研发有效的戒烟药物具有重要意义。尼古丁成瘾过程与神经系统中数量众多的基因/蛋白质相关。目前已检测出大量与该过程相关的基因/蛋白质，从中确定在尼古丁成瘾过程中起主要作用的分子以及相关的信号通路，是尼古丁成瘾研究的主要问题之一。本项目将收集由遗传相关分析、连锁分析、高通量表达分析和其他类型研究所确认的与尼古丁在神经系统中作用相关的基因/蛋白质，并与其结构、功能等方面的信息整合。依据这些信息，建立评估基因/蛋白质与尼古丁成瘾相关性的算法，用以筛选在尼古丁成瘾过程中起主要作用的基因/蛋白质。以所筛选分子为基础，寻找与尼古丁成瘾相关的信号通路和分子作用网络。通过分析主要的信号通路和分子作用网络，探索尼古丁对基因/蛋白质以及相关信号通路的调控路径和方式。在此基础上构建包括多方面信息的尼古丁成瘾过程的分子机理模型，并通过分析分子作用网络确定可能的治疗尼古丁成瘾药物作用靶点。

中文关键词： 尼古丁；基因；成瘾；信号通路；分子机理

英文摘要： Investigating the molecular mechanism underlying nicotine addiction is fundamental for developing more effective drugs that can help smokers achieve and sustain abstinence from smoking. It has been shown that in the nervous system, a large number of genes/proteins may be involved in the initiation and development of nicotine addiction. Recent years, many of these genes/proteins potentially associated with nicotine addiction have been reported. How to screen these candidates to identify the key components, as well as recognize the major enriched signaling pathways, remains a major hurdle in exploring the molecular mechanisms related to nicotine addiction. Here we propose to use a multi-dimensional evidence-based approach to prioritize genes/proteins involved in nicotine addiction, in which genes/proteins will be collected and curated from four different categories,i.e.,association studies, linkage analysis, high-throughput expression analysis, as well as literature search for other types of analysis. The collected information will be fused and integrated with the structural and functional data related to the genes/proteins collected.Based on such information,we will develop a scoring system to measure the correlation between each gene/protein with nicotine addiction, with which we will rank and prioritize the gen

英文关键词： Nicotine；Gene；Addiction；Signaling pathway；Molecular mechanism