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: 2892472
• 负责人: ANNE B YOUNG
• 金额: $ 157.12万
• 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/2892472
• 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.

为了响应RFA NS-98-001提交的提交中心将研究如何异常 α-突触核蛋白的贩运，这可能涉及两种新型蛋白 （Parkin和Torsina），导致多巴胺神经元死亡 帕金森氏病。我们还将研究基底神经节的性质 帕金森主义引起的功能障碍，我们将使用这些技术 开发以验证我们的分子机制模型。四个项目 并将涉及两个核心。第一个项目，在布拉德利博士的领导下 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，在博士的领导下 Xandra Breakefield将使用分子生物学技术来确定 α-突触核蛋白基因不同等位基因的程度， 帕金（Parkin），托西娜（Torsina 对于快速发作的肌张力障碍，帕金森主义有助于 对帕金森氏病的敏感性。第三个项目，约翰博士 彭尼（Penney）将确定最脆弱的多巴胺神经元是 这些潜在致病性负担最高的人 使用双标签原位杂交和反义RNA的分子 技术。在安·格雷比尔（Ann Graybiel）博士领导下的第四个项目将重点关注 确定帕金森主义和α-的神经系统后果 使用Tetrode的实验动物中突触核蛋白和肌张力障碍突变 录音。这些项目高度整合，每个项目交互 与其他所有人都广泛地为整个计划做出贡献。这 中心将得到行政核心和重要的培训的支持 和临床核心，将为下一个提供一流的训练场 帕金森氏病研究人员产生。最后，两个 涉及的机构确保中心将存在于高度 支持环境。