α-Synuclein-derived lipoparticles in the study of α-Synuclein amyloid fibril formation

Aggregation of the protein alpha-Synuclein (alpha Syn) is of great interest due to its involvement in the pathology of Parkinson's disease. However, under in vitro conditions alpha Syn is very soluble and kinetically stable for extended time periods. As a result, most alpha Syn aggregation assays rely on conditions that artificially induce or enhance aggregation, often by introducing rather non-native conditions. It has been shown that alpha Syn interacts with membranes and conditions have been identified in which membranes can promote as well as inhibit alpha Syn aggregation. It has also been shown that alpha Syn has the intrinsic capability to assemble lipid-protein-particles, in a similar way as apolipoproteins can form lipid-bilayer nanodiscs. Here we show that these alpha Syn-lipid particles (alpha Syn-LiPs) can also effectively induce, accelerate or inhibit alpha Syn aggregation, depending on the applied conditions. alpha Syn-LiPs therefore provide a general platform and additional tool, complementary to other setups, to study various aspects of alpha Syn amyloid fibril formation.