Structural and pathological consequences of aSyn/lipid membrane interactions

aSyn/脂膜相互作用的结构和病理后果

• 批准号: 2594981
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2594981
• 关键词: Structural; pathological; consequences; aSyn; lipid

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.

脂质膜在我们身体的生物和病理过程中起着关键作用。脑中几种神经退行性蛋白质聚集体的形成通过这些蛋白质与脂质的相互作用来调节[Nat. Chem. 2018，10，673]。特别地，α-突触核蛋白（aSyn）聚集体与帕金森病（PD）和痴呆相关，并且作为单体与神经元膜相互作用的直接结果而形成。目前，我们仍然缺乏关于这一进程机制的信息。我们项目的目标是确定各种脂质影响aSyn聚集体的形成、结构和毒性的机制，以及聚集体如何影响神经元膜。我们将通过结合抗体发现，荧光环境探针和单分子检测来做到这一点。该项目不仅将揭示PD和其他形式痴呆症的关键病理机制，还将提供有关蛋白质-脂质相互作用的基础物理知识，并为生物分子带来新的超灵敏检测方法。