Peptides as modulators of α-synuclein aggregation

Α-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 aβ-peptide aggregation,to cross-react with α-synuclein interfering with its fibril formation. the influence of the mephe topography on the interaction with α-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 α-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. © 2015 bentham science publishers.