Peptides as modulators of α-synuclein aggregation(20 views) Ruzza P, Gazziero M, Marchi MD, Massalongo G, Marchiani A, Autiero I, Tessari I, Bubacco L, Calderan A
Protein Pept Lett (ISSN: 0929-8665linking), 2015; 22
(4
): 354-361.
Affiliations: Biomolecular Chemistry of CNR, Padova Unit, Via F. Marzolo n.1 - 33131 Padova, Italy. paolo.ruzza@cnr.it.
References: Not available.
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.