Inhibition of α-Synuclein Amyloid Fibril Elongation by Blocking Fibril Ends.

摘要: Misfolding of the protein α-synuclein (αSyn) into amyloid fibrils plays a central role in development Parkinson's disease. Most approaches for inhibition αSyn fibril formation are based on stabilizing native monomeric form or destabilizing fibrillized misfolded form. They require high concentrations inhibitor and therefore cannot be easily used therapies. In this work, we designed an (Inh-β) that selectively binds growing ends creates steric hindrance binding αSyn. This approach permits at Inh-β (IC50 =850 nm) much lower than concentration We studied its kinetic mechanism in vitro identified reactions limit efficiency. It is shown blocking effective to inhibiting growth provides insights inhibitors aggregation.