Loss in Toxic Function of Aggregates of α -Synuclein Mutants by a β-Synuclein Derived Peptide

Title:Loss in Toxic Function of Aggregates of α -Synuclein Mutants by a β-Synuclein Derived Peptide

Volume: 24 Issue: 8

Author(s): Soheila Mohammadi, Maryam Nikkhah*Saman Hosseinkhani

Affiliation:

• Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, 14115-154,Iran

Keywords: α-Synuclein, aggregation, amyloid fibrils, peptide inhibitor, cell toxicity, Parkinson's disease.

Abstract: 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 cytometry.

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.

Cite this article as:

Mohammadi Soheila , Nikkhah Maryam *, Hosseinkhani Saman , Loss in Toxic Function of Aggregates of α -Synuclein Mutants by a β-Synuclein Derived Peptide, Protein & Peptide Letters 2017; 24 (8) . https://dx.doi.org/10.2174/0929866524666170818154033