Molecular cell biology of hNP22: role in alcohol dependence

我们使用差异筛选程序来检测人类酒精中毒大脑中基因表达的变化，并描述了一个新的基因，我们将其命名为hNP22，该基因在酒精中毒病例的额叶上皮质区表达增加。这是从人脑中分离出的一种新的酒精反应基因的首次报道。我们现在建议进一步探索hNP22基因、其产物及其在人脑组织中的调控，以及在各种实验系统中的作用。我们将确定蛋白质表达如何与饮酒水平相关。我们将使用动物和细胞培养模型来确定该基因对各种刺激的反应。我们将对重组蛋白进行表达，以确定其功能。该基因产物很可能是神经细胞内重要信号通路的一个组成部分，因此可能是治疗干预的新靶点。

We used a differential screening procedure to detect changes in gene expression in the human alcoholic brain and described a novel gene, which we named hNP22, with increased expression in the superior frontal cortex of the alcoholic cases. This is the first report of a novel alcohol-responsive gene isolated from the human brain. We now propose to further explore the hNP22 gene, its product and its regulation in human brain tissue, and in a variety of experimental systems. We will determine how protein expression correlates with the level of alcohol consumption. We will use animal and cell culture models to determine the response of the gene to various stimuli. We will express the recombinant protein to determine its function. It is likely that the gene product may be a component in an important signal pathway within neuronal cells and thus may represent a novel target for therapeutic intervention.