This project examined the molecular mechanisms by which alpha-synuclein, a key protein implicated in Parkinson’s disease, interacts with lipid membranes and forms amyloid fibrils, the main components of Lewy bodies found in affected neurons. Using small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS), the research characterized the structures of alpha-synuclein in both its monomeric and fibrillar states, as well as its interactions with different model lipid systems.
The studies revealed that monomeric alpha-synuclein deforms lipid micelles, with partial recovery upon fibril formation, and that fibrillation can induce vesicle fusion without incorporating lipids into the fibril structure. Moreover, colloidally unstable fibrils were found to cluster independently of the surrounding lipid environment.
By combining neutron and X-ray scattering, this work provided new structural insights into the protein–membrane interactions underlying amyloid formation, contributing to a better understanding of the molecular processes involved in Parkinson’s disease.