Single-vesicle imaging reveals lipid-selective and stepwise membrane disruption by monomeric α-synuclein
Artikel i vetenskaplig tidskrift, 2020
Neurodegenerative diseases are increasing among the world's population, but there are no cures. These disorders all involve proteins that assemble into amyloid fibers which results in brain cell death. Evidence suggests that association of these proteins with lipid membranes is crucial for both functional and pathological roles. In Parkinson's disease, the involved protein, α-synuclein, is thought to function in trafficking of lipid vesicles in the brain. In search of mechanistic origins, increasing focus is put on identifying neurotoxic reactions induced by membrane interactions. To contribute new clues to this question, we here employed a new surface-sensitive scattering microscopy technique. With this approach, we discovered that α-synuclein perturbs vesicles in a stepwise and lipid-dependent fashion already at very low protein coverage.