Self-oligomerization and protein aggregation of α-synuclein in the presence of coomassie brilliant blue

27Citations
Citations of this article
35Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

α-Synuclein has been implicated in various neuro-degenerative disorders, including Parkinson's and Alzheimer's diseases, by its participation in abnormal protein depositions. As the protein has been suggested to play a significant role in the formation of the deposits which might be responsible for neurodegeneration, there is a strong demand to screen for α-synuclein-interactive small molecules. In this report, Coomassie Brilliant Blue (CBB) interaction of α-synuclein has been investigated with respect to induction of protein self-oligomerization in the presence of the chemical coupling reagent N-(ethoxy-carbonyl)-2-ethoxy-1,2-dihydroquinoline. Both CBB-G and CBB-R, which differ by only two methyl groups, induced the self-oligomerization of α-synuclein in a biphasic manner with optimal dye concentrations of 250 μm and 150 μm, respectively. The protein aggregates of α-synuclein induced by the dyes in the absence of the coupling reagent were analysed by electron microscopy. Whereas CBB-G induced formation of protein aggregates with a worm-like structure, CBB-R induced clear fibrilization of α-synuclein on a background of granular structures. CBB-R interacted with α-synuclein approximately twice as effectively as CBB-G (dissociation constants 0.63 μm and 1.37 μm, respectively). These dye interactions were independent from the acidic C-terminus of α-synuclein, which was reminiscent of the Aβ25-35 interaction of α-synuclein. However, the metal-catalysed oxidative self-oligomerization of α-synuclein in the presence of Cu2+/H2O2, which was augmented synergistically by Aβ25-35, was not affected by the dyes. This indicates that the dye binding site is also distinctive from the Ab25-35 interaction site on α-synuclein. These biochemically specific interactions between α-synuclein and the dyes indicate that α-synuclein-interactive small molecules could provide a tool with which to approach development of diagnostic, preventive, or therapeutic strategies for various α-synuclein-related neurodegenerative disorders.

Cite

CITATION STYLE

APA

Lee, D., Lee, E. K., Lee, J. H., Chang, C. S., & Paik, S. R. (2001). Self-oligomerization and protein aggregation of α-synuclein in the presence of coomassie brilliant blue. European Journal of Biochemistry, 268(2), 295–301. https://doi.org/10.1046/j.1432-1033.2001.01877.x

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free