Basic mechanisms of autophagy in neuroprotection and neurodegeneration

自噬在神经保护和神经退行性疾病中的基本机制

• 批准号: 141333858
• 负责人: Dr. Angelika Rambold
• 金额: --
• 依托单位: Janelia Research Campus
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/141333858?language=en
• 关键词: Basic; mechanisms; autophagy; neuroprotection; neurodegeneration

Autophagy is a highly dynamic cellular degradation pathway with the capacity to remove aggregated proteins and damaged organelles such as mitochondria from cells. The autophagosomal pathway is important for cellular survival under basal conditions but its essential role becomes even more evident in pathological processes. Several studies implicate autophagy as a beneficial system preventing from neuronal cell death in models of neurodegenerative disorders. However, the mechanism how autophagy mediates its protective effect under disease and physiological conditions is currently unclear.Therefore, I propose to address this fundamental question applying high-resolution and time-lapse fluorescent microscopy techniques to gain insight into the autophagosomal turnover of protein aggregates and mitochondria. Firstly, I will investigate the determinants for autophagosomal degradation of aggregates in means of aggregate dynamics and composition in disease models. Secondly, I will analyze the impact of mitochondrial function and their autophagosomal turnover on cell toxicity.

自噬是一种高度动态的细胞降解途径，能够从细胞中去除聚集的蛋白质和受损的细胞器，如线粒体。自噬体途径对于基础条件下的细胞存活是重要的，但其基本作用在病理过程中变得更加明显。一些研究暗示自噬是在神经退行性疾病模型中防止神经元细胞死亡的有益系统。然而，在疾病和生理条件下，自噬如何介导其保护作用的机制目前还不清楚，因此，我建议解决这个基本问题，应用高分辨率和延时荧光显微镜技术，以深入了解蛋白质聚集体和线粒体的自噬体周转。首先，我将通过疾病模型中聚集体的动力学和组成来研究自噬体降解聚集体的决定因素。其次，我将分析线粒体功能及其自噬体周转对细胞毒性的影响。