Pathogenesis of neurodegenerative disorders: The role of alpha-Synuclein in vesicular transport systems

神经退行性疾病的发病机制：α-突触核蛋白在囊泡运输系统中的作用

• 批准号: 5397105
• 负责人: Professor Dr. Jochen Klucken
• 金额: --
• 依托单位: Charlestown Healthcare Center
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2005-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5397105?language=en
• 关键词: Pathogenesis; neurodegenerative; disorders; role; alpha

Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and the dementia with Lewy bodies (DLB) gain growing importance in the increasing aged population. Lewy bodies (LBs) are observed in these diseases. PD and DLB have been recently categorized as "synucleiopathies" since LBs are mainly composed of insoluble a-synuclein protein aggregates. Despite the genetic linkage of alpha-synuclein to rare familial PD, its function remains unknown. Recently, an association of a-synuclein with vesicular transport processes was suggested. a-Synuclein binds to lipid membranes and synthetic vesicles and associates with key proteins of the synaptic vesicle recycling machinery and the axonal vesicular transport system. The aims of the phase I of the Emmy NoetherProgramm are: (I) to characterize the interactions of alphasynuclein with vesicle associated proteins and lipids, (II) to functionally evaluate the role of a-synuclein in vesicular transport processes in vitro and; (III) to assess these findings of the aim I and II in vivo, both in transgenic mice and in brain samples of PD, DLB, or AD. These experiments will help to clarify the role of alpha-synuclein in neuronal vesicular transport and provide an ideal tool of identify future therapeutic stratgies that will be the focus of phase II of the Emmy Noether-Programm.

神经退行性疾病如阿尔茨海默病（AD）、帕金森病（PD）和路易体痴呆（DLB）在日益增长的老年人口中变得越来越重要。在这些疾病中观察到路易体（LB）。PD和DLB最近被归类为“突触核蛋白病”，因为LB主要由不溶性α-突触核蛋白蛋白聚集体组成。尽管α-突触核蛋白与罕见的家族性PD有遗传联系，但其功能仍然未知。最近，一个协会的α-突触核蛋白与囊泡运输过程的建议。α-突触核蛋白与脂质膜和合成囊泡结合，并与突触囊泡再循环机制和轴突囊泡转运系统的关键蛋白质缔合。Emmy NoetherTM第I阶段的目的是：（I）表征突触核蛋白与囊泡相关蛋白和脂质的相互作用，（II）在功能上评估α-突触核蛋白在体外囊泡转运过程中的作用，以及;（III）在转基因小鼠和PD、DLB或AD的脑样品中评估体内目的I和II的这些发现。这些实验将有助于阐明α-突触核蛋白在神经元囊泡转运中的作用，并为确定未来的治疗策略提供理想的工具，这将是Emmy Noether-Bullummm第二阶段的重点。