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A routinely used protein staining dye acts as an inhibitor of wild type and mutant alpha-synuclein aggregation and modulator of neurotoxicity

Ahsan, Nuzhat and Siddique, Ibrar Ahmed and Gupta, Sarika and Surolia, Avadhesha (2018) A routinely used protein staining dye acts as an inhibitor of wild type and mutant alpha-synuclein aggregation and modulator of neurotoxicity. In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 143 . pp. 1174-1184.

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Official URL: http://dx.doi.org/10.1016/j.ejmech.2017.10.002

Abstract

Inhibition of amyloid formation along with modulation of toxicity employing small molecules is emerging as a potential therapeutic approach for protein misfolding disorders which includes Parkinson's disease, Alzheimer's disease and Multiple System Atrophy etc. Countless current interventional strategies for treating alpha-synucleinopathies consider using peptidic and non-peptidic inhibitors for arresting fibrillisation, disrupting existing fibrils and reducing associated toxicity. One group of molecules less exploited in this regard are triphenylmethane dyes. Herein we tested the inhibitory effect of two routinely used protein staining dyes viz Coomassie Brilliant blue G (CBBG) and Coomassie Brilliant blue R (CBBR) employing several biophysical and cell based methods. Our results showed that both the dyes not only efficiently inhibit fibrillisation but also disrupt existing fibrils. Nonetheless, only CBBR prevented the appearance of A11 epitopes which are marker of toxicity. Moreover, CBBR was also able to stall fibrillisation of A53T mutant alpha-synuclein and reduce associated neurotoxicity. This study thus reports the potential of CBBR as a therapeutic molecule. (C) 2017 Elsevier Masson SAS. All rights reserved.

Item Type: Journal Article
Additional Information: Copy right for this article belong to the ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 23 RUE LINOIS, 75724 PARIS, FRANCE
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Depositing User: Id for Latest eprints
Date Deposited: 02 Mar 2018 15:03
Last Modified: 02 Mar 2018 15:03
URI: http://eprints.iisc.ac.in/id/eprint/58960

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