Background: Parkinson's disease (PD) primarily results from a severe and selective
damage of dopaminergic neurons. The neuropathological hallmark of the disease is the presence of
protein inclusions of α-Synuclein (αS) within the surviving neurons. To date, several researchers
have been focused on screening for the inhibitors that are able to block, slow down, or reverse αS
aggregation, particularly at its early stages.
Objectives: In this work, we aimed to investigate the effects of a β-Synuclein derived peptide on
oligomerization of pathological mutants of αS (A53T, A30P, E46K).
Method: The effects of the peptide on aggregation of native and mutant of αS were examined by
fluorescence spectroscopy and electron microscopy. The influence of the peptide inhibitor on cell
toxicity of aggregation products of αS and its mutants were investigated by MTT assay and flow
Results: It was shown that the peptide inhibitor effectively blocks the fibrillation of not only the
native αS but also the PD related αS mutants in vitro, suggesting a similar mechanism of oligomerization
for native and mutants of αS. The peptide inhibitor greatly diminished the cell toxicity of the
aggregation products of native and mutants of αS.
Conclusion: Our findings suggest the therapeutic potential of this peptide for treatment of the rare
inherited forms of PD.