Lipid droplet binding and oligomerization properties of the Parkinson's disease protein α-synuclein

摘要: α-Synuclein is a major component of the fibrillary lesion known as Lewy bodies and neurites that are pathologic hallmarks Parkinson's disease (PD). In addition, point mutations in α-synuclein gene imply dysfunction pathology inherited forms PD. member family proteins found primarily brain concentrated within presynaptic terminals. Here, we address localization membrane binding characteristics wild type PD mutants cultured cells. cells treated with high concentrations fatty acids, accumulated on phospholipid monolayers surrounding triglyceride-rich lipid droplets was able to protect stored triglycerides from hydrolysis. mutant synucleins showed variable distributions were less effective regulating triglyceride turnover. Chemical cross-linking demonstrated synuclein formed small oligomers cells, dimers trimers, preferentially associated cell membranes. Our results suggest initial phases aggregation may occur surfaces membranes pathological conditions induce enhance propensity for subsequent aggregation.