Peptides as modulators of alpha-synuclein aggregation

?-Synuclein forms amyloid deposits in the dopaminergic neurons; a process that is believed to contribute to the Parkinson's disease. An emerging theme in amyloid research is the hypothesis that the toxic species produced during amyloid formation share common physic-chemical features and exert their effects by common modes. This prompted the idea that molecules able to inhibit a protein aggregation process may cross-react with other amyloidogenic proteins, interfering in their fibrils formation. We investigate the ability of analogues of the heptapeptide H-Arg-Lys-Val-MePhe-Tyr-Thr-Trp-OH2, an inhibitor of A?-peptide aggregation, to cross-react with ?-synuclein interfering with its fibril formation. The influence of the MePhe topography on the interaction with ?-synuclein has also been evaluated, replacing the MePhe residue with either Phe or the conformationally restricted Tic residues. Peptides interact with good affinity with the ?-synuclein monomer, promoting its aggregation process. This work provides the basis for the development of new drugs based on peptidomimetics able to modify the oligomers-mature fibrils equilibrium towards this last species.