PHARMACOLOGICAL REGULATION OF BASAL GANGLIA ENRICHED PHOSPHOPROTEIN

基底节富含磷酸蛋白的药理调节

• 批准号: 6273396
• 负责人: GRETCHEN L SNYDER
• 金额: $ 29.2万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6273396
• 关键词: basal ganglia; biological signal transduction; casein kinase; cell line; dopamine; enzyme activity; gene targeting; genetically modified animals; human tissue; laboratory mouse; laboratory rat; phosphatase inhibitor; phosphoprotein phosphatase; phosphoproteins; phosphorylation; postmortem; protein kinase; psychopharmacology; schizophrenia; tissue /cell culture

This project will seek to examine protein phosphorylation pathways in the basal ganglia which mediate the actions of dopamine in normal and abnormal brain function. The pharmacological regulation of phosphoproteins enriched in the basal ganglia will be studied using intact cell preparations derived from basal ganglia structures of normal animals (e.g., neostriatal slices, primary neostriatal cell cultures, synaptosomes) or in immortalized cells which mimic various physiological properties of basal ganglia neurons. In addition, the regulation of these phosphoproteins under physiological conditions will be studied by administration of drugs to normal, intact animals and the subsequent analysis of the phosphorylated proteins in the brains of these animals. The goal of these studies is to identify first messenger and signal transduction pathways which play a significant role in regulating the function of basal ganglia phosphoproteins in the intact animal. Some of these studies will seek to identify signaling pathways which regulate phosphoproteins by using transgenic animals, which express mutagenized phosphoproteins, or genetically-altered animals, which are deficient in cell signaling molecules. Finally, the levels of phosphoproteins and associated signaling molecules will be measured in post-mortem brain tissue from normal individuals and patients with schizophrenia, in order to assess the possible involvement of phosphoproteins and their regulatory pathways in this dopamine-associated brain disorder. It is anticipated that these studies will provide an essential understanding of dopamine-mediated protein phosphorylation in the normal brain and the possible role of this process in dopamine-mediated motor and psychiatric disease.

该项目将寻求检查蛋白质磷酸化途径