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Title: Thioflavin-S staining of bacterial inclusion bodies for the fast, simple, and inexpensive screening of amyloid aggregation inhibitors
Author: Pouplana, Sergi
Espargaró Colomé, Alba
Galdeano Cantador, Carlos
Viayna, Elisabet
Sola, Irene
Ventura, Salvador
Muñoz-Torrero López-Ibarra, Diego
Sabaté Lagunas, Raimon
Keywords: Malalties neurodegeneratives
Malaltia d'Alzheimer
Disseny de medicaments
Compostos heterocíclics
Neurodegenerative Diseases
Alzheimer's disease
Drug design
Heterocyclic compounds
Issue Date: Mar-2014
Publisher: Bentham Science Publishers
Abstract: Amyloid aggregation is linked to a large number of human disorders, from neurodegenerative diseases as Alzheimer"s disease (AD) or spongiform encephalopathies to non-neuropathic localized diseases as type II diabetes and cataracts. Because the formation of insoluble inclusion bodies (IBs) during recombinant protein production in bacteria has been recently shown to share mechanistic features with amyloid self-assembly, bacteria have emerged as a tool to study amyloid aggregation. Herein we present a fast, simple, inexpensive and quantitative method for the screening of potential anti-aggregating drugs. This method is based on monitoring the changes in the binding of thioflavin-S to intracellular IBs in intact Eschericchia coli cells in the presence of small chemical compounds. This in vivo technique fairly recapitulates previous in vitro data. Here we mainly use the Alzheimer"s related beta-amyloid peptide as a model system, but the technique can be easily implemented for screening inhibitors relevant for other conformational diseases simply by changing the recombinant amyloid protein target. Indeed, we show that this methodology can be also applied to the evaluation of inhibitors of the aggregation of tau protein, another amyloidogenic protein with a key role in AD.
Note: Versió postprint del document publicat a:
It is part of: Current Medicinal Chemistry, 2014, vol. 21, num. 9, p. 1152-1159
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ISSN: 0929-8673
Appears in Collections:Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
Articles publicats en revistes (Institut de Biomedicina (IBUB))

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