Since the connection between PREP and alpha-synuclein aggregation was found and published on 2008, one of the mysteries has been if these two proteins interact? When DiDaniel et al. published their findings on PREP knock-out animal on 2009, they also showed that PREP can form protein-protein interactions and its enzymatic activity is not needed for that. However, the interaction with alpha-synuclein, and the mechanism how PREP affects alpha-synuclein aggregation remained unclear.

Now we have revealed in collaboration with Dr. Henri Huttunen’s group (Neuroscience Center, University of Helsinki) that PREP can directly interact with alpha-synuclein, and this interaction is critical for alpha-synuclein aggregation. The interaction was verified by using pure proteins and also a cellular model of interactions. Importantly, we also showed that PREP inhibition modifies the structure of PREP by stabilizing a compact form of PREP that then binds alpha-synuclein tighter to itself leading to decreased aggregation process. The results were published in Journal of Biological Chemistry, and you can read the paper or at least the abstract from here.