title: Peptides as modulators of α-synuclein aggregation.
abstract: 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.
authors: Biomolecular Chemistry of CNR, Padova Unit, Via F. Marzolo n.1 - 33131 Padova, Italy. paolo.ruzza@cnr.it.
authors: Paolo
authors: P
authors: Ruzza
authors: Matteo
authors: M
authors: Gazziero
authors: Maria De
authors: MD
authors: Marchi
authors: Giada
authors: G
authors: Massalongo
authors: Anna
authors: A
authors: Marchiani
authors: Ida
authors: I
authors: Autiero
authors: Isabella
authors: I
authors: Tessari
authors: Luigi
authors: L
authors: Bubacco
authors: Andrea
authors: A
authors: Calderan
mesh_terms: D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D066329:Protein Aggregates; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010455:Peptides; D066329:Protein Aggregates; D051844:alpha-Synuclein