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

A routinely used protein staining dye acts as an inhibitor of wild type and mutant... 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 α-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 α-synuclein and reduce associated neurotoxicity. This study thus reports the potential of CBBR as a therapeutic molecule. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Medicinal Chemistry Elsevier

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

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Publisher
Elsevier
Copyright
Copyright © 2017 Elsevier Masson SAS
ISSN
0223-5234
eISSN
1768-3254
D.O.I.
10.1016/j.ejmech.2017.10.002
Publisher site
See Article on Publisher Site

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 α-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 α-synuclein and reduce associated neurotoxicity. This study thus reports the potential of CBBR as a therapeutic molecule.

Journal

European Journal of Medicinal ChemistryElsevier

Published: Jan 1, 2018

References

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