%0 Journal Article
%T Blocking the FKBP12 induced dendrimeric burst in aberrant aggregation of ¦Á-synuclein by using the ElteN378 synthetic inhibitor
%A Gabriella Caminati
%A Maria Raffaella Martina
%A Piero Procacci
%A Stefano Menichetti
%J Journal of Enzyme Inhibition and Medicinal Chemistry
%D 2019
%R https://doi.org/10.1080/14756366.2019.1667342
%X Abstract ¦Á-Synuclein (¦Á-syn), a disordered cytoplasmatic protein, plays a fundamental role in the pathogenesis of Parkinson¡¯s disease (PD). Here, we have shown, using photophysical measurements, that addition of FKBP12 to ¦Á-syn solutions, dramatically accelerates protein aggregation, leading to an explosion of dendritic structures revealed by fluorescence and phase-contrast microscopy. We have further demonstrated that this aberrant ¦Á-syn aggregation can be blocked using a recently discovered non-immunosuppressive synthetic inhibitor of FKBP12, ElteN378. The role of FKBP12 and of ElteN378 in the ¦Á-syn aggregation mechanism has been elucidated using molecular dynamics simulations based on an effective coarse-grained model. The reported data not only reveal a new potent synthetic drug as a candidate for early stage treatment of ¦Á-syn dependent neurodegenerations but also pave the way to a deeper understanding of the mechanism of action of FKBP12 on ¦Á-syn oligomeric aggregation, a topic which is still controversial
%U https://www.tandfonline.com/doi/full/10.1080/14756366.2019.1667342