α-Synuclein is the main protein component associated with Parkinson’s disease. It can adopt various structures and these lead to aggregates that differ in toxicity. The structural differences between the aggregates are still unclear. α-Synuclein fibrils are found in the brains of patients that suffer from Parkinson’s disease (PD). How PD pathology spreads in the brain is unknown.
This project focuses on the study of α-synuclein fibril formation and fibril structure. High-resolution transmission electron microscopy (TEM) is employed.
Many neurodegenerative diseases are linked to protein aggregation. The misfolding of endogenous proteins and their assembly into insoluble fibril structures, called amyloids, is linked to neuronal degeneration. This misfolding can trigger healthy proteins to adopt a misfolded structure, which leads to a stereotypic and progressive spreading of the protein aggregation through the brain. α-Synuclein is a 140-residue, cytoplasmic membrane-attached protein that is found in the pre-synaptic terminals of neurons. Misfolding of α-synuclein is linked to a range of debilitating diseases known as the synucleinopathies. These include multiple system atrophy, dementia with Lewy bodies and Parkinson's disease.
This project focuses on the study of α-synuclein fibril formation and their structure using high-resolution transmission electron microscopy (TEM). Starting from monomeric α-synuclein, fibril formation is induced by exposing the protein to different hydrophobic-hydrophilic interfaces. In order to achieve α-synuclein fibrils that differ in shape and size, different chemicals and lipids are added. The target is to determine the structure of the different α-synuclein fibrils formed in vitro and relate these forms to PD and the other synucleinopathies.