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.

journal_name

Protein Pept Lett

authors

Ruzza P,Gazziero M,Marchi MD,Massalongo G,Marchiani A,Autiero I,Tessari I,Bubacco L,Calderan A

doi

10.2174/0929866522666150209142649

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

354-61

issue

4

eissn

0929-8665

issn

1875-5305

pii

PPL-EPUB-65075

journal_volume

22

pub_type

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