Structural and pathological consequences of aSyn/lipid membrane interactions

点击翻译按钮获取中文摘要

Lipid membranes play a key role in biological and pathological processes of our body. The formation of aggregates of several neurodegenerative proteins in the brain is modulated by the interaction of these proteins with lipids [Nat. Chem. 2018, 10, 673]. In particular, alpha-synuclein (aSyn) aggregates are linked to Parkinson's disease (PD) and dementia and form as a direct consequence of the monomer interaction with neuronal membranes. Currently, we still lack information regarding the mechanism of this process. The goal of our project is to determine the mechanisms by which various lipids affect the formation, structure and toxicity of aSyn aggregates and, in turn, how aggregates affect neuronal membranes. We will do so by combining antibody-discovery, fluorescent environmental probes, and single-molecule detection. This project will not only unveil key pathological mechanism in PD and other forms of dementia, but will also provide foundational physical knowledge on protein-lipid interactions and lead to new ultrasensitive detection methods for biomolecules.