Influence Of Lipid Membranes On Alpha-Synuclein Aggregation

alpha-Synuclein is a neuronal protein involved in synaptic vesicle trafficking. During the course of Parkinson's disease, it aggregates, forming amyloid fibrils that accumulate in the midbrain. This pathological fibrillization process is strongly modulated by physiological interactions of alpha-synuclein with lipid membranes. However, the detailed mechanism of this effect remains unclear. In this work, we used environment-sensitive fluorescent dyes to study the influence of model lipid membranes on the kinetics of alpha-synuclein fibrillization. We observed that formation of the fibrils from alpha-synuclein monomers is strongly delayed even by small amounts of lipids. Furthermore, we found that membrane-bound alpha-synuclein monomers are not involved in fibril elongation. Hence, presence of lipids slows down fibril growth proportionally to the fraction of membrane-bound protein.