MGH/MIT PARKINSONS DISEASE RESEARCH CENTER

麻省总医院/麻省理工学院帕金森病研究中心

• 批准号: 6040964
• 负责人: John B Penney
• 金额: $ 14.45万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6040964
• 关键词: Parkinson's disease; alpha synuclein; pathologic process

Submitted in response to RFA NS-98-001 this center will study how aberrant trafficking of alpha-synuclein, which may involve the two novel proteins (parkin and torsinA), leads to the death of dopamine neurons in Parkinson's disease. We will also study the nature of the basal ganglia dysfunction caused by parkinsonism and we will use the techniques so developed to validate our models of molecular mechanisms. Four projects and two cores will be involved. The first project, under Dr. Bradley Hyman, will determine the role of alpha-synuclein in Lewy body formation using transgenic animals and confocal microscopy. The second, under Dr. Xandra Breakefield, will use molecular biological techniques to determine the degree to which different alleles of the genes for alpha-synuclein, parkin, torsinA, which is mutated in early onset torsion dystonia, and that for Rapid Onset Dystonia Parkinsonism contribute to the susceptibility to Parkinson's disease. The third project, under Dr. John Penney, will determine if the most vulnerable dopamine neurons are the ones that bear the highest burden of these potentially pathogenic molecules using double-label in situ hybridization and antisense RNA techniques. The fourth project, under Dr. Ann Graybiel, will focus on determining the neural systems consequences of parkinsonism and the alpha- synuclein and dystonia mutations in experimental animals using tetrode recordings. The projects are highly integrated, each interacting extensively with all the others to contribute to the overall program. The center will be supported by an administrative core and a vital, training and clinical core that will provide a superb training ground for the next generation of parkinson's disease researchers. Finally, the two institutions involved ensure that the center will exist in a highly supportive environment.

响应 RFA NS-98-001 提交，该中心将研究异常情况如何 α-突触核蛋白的运输，可能涉及两种新蛋白质 （parkin 和 torsinA），导致多巴胺神经元死亡 帕金森病。我们还将研究基底神经节的性质 帕金森症引起的功能障碍，我们将使用这些技术 开发用于验证我们的分子机制模型。四个项目 并且会涉及两个核心。第一个项目，由布拉德利博士领导 海曼将确定α-突触核蛋白在路易体形成中的作用 使用转基因动物和共聚焦显微镜。第二个是在博士的指导下。 Xandra Breakefield 将使用分子生物学技术来确定 α-突触核蛋白基因的不同等位基因的程度， Parkin、torsinA，在早发性扭转肌张力障碍中发生突变，以及 快速发作的肌张力障碍帕金森症有助于 易患帕金森病。第三个项目，由约翰博士负责 彭尼将确定最脆弱的多巴胺神经元是否是 那些承受这些潜在致病性负担最重的人 使用双标记原位杂交和反义RNA分子 技术。第四个项目由 Ann Graybiel 博士领导，重点关注 确定帕金森症和α-的神经系统后果 使用 tetrode 实验动物中的突触核蛋白和肌张力障碍突变 录音。这些项目高度集成，相互影响 与所有其他人广泛合作，为整个计划做出贡献。这 中心将得到一个行政核心和一个重要的培训中心的支持 和临床核心，将为下一代提供极好的训练场 一代帕金森病研究人员。最后，两人 相关机构确保该中心将在高度 支持性环境。