Basic mechanisms of autophagy in neuroprotection and neurodegeneration

• Applicant: Dr. Angelika Rambold
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2009 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 141333858

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.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Jennifer Lippincott-Schwartz, Ph.D.