Using bacterial inclusion bodies to screen for amyloid aggregation inhibitors.

Microbial Cell Factories
Anna Villar-PiquéSalvador Ventura

Abstract

The amyloid-β peptide (Aβ42) is the main component of the inter-neuronal amyloid plaques characteristic of Alzheimer's disease (AD). The mechanism by which Aβ42 and other amyloid peptides assemble into insoluble neurotoxic deposits is still not completely understood and multiple factors have been reported to trigger their formation. In particular, the presence of endogenous metal ions has been linked to the pathogenesis of AD and other neurodegenerative disorders. Here we describe a rapid and high-throughput screening method to identify molecules able to modulate amyloid aggregation. The approach exploits the inclusion bodies (IBs) formed by Aβ42 when expressed in bacteria. We have shown previously that these aggregates retain amyloid structural and functional properties. In the present work, we demonstrate that their in vitro refolding is selectively sensitive to the presence of aggregation-promoting metal ions, allowing the detection of inhibitors of metal-promoted amyloid aggregation with potential therapeutic interest. Because IBs can be produced at high levels and easily purified, the method overcomes one of the main limitations in screens to detect amyloid modulators: the use of expensive and usually highly insoluble synt...Continue Reading

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Citations

Jan 1, 2013·Microbial Cell Factories·Anna Villar-Piqué, Salvador Ventura
Feb 16, 2013·Microbial Cell Factories·Diletta AmiSilvia Maria Doglia
Oct 10, 2013·Critical Reviews in Biotechnology·Neus Ferrer-MirallesAntonio Villaverde
Nov 19, 2015·Biotechnology Journal·Anna Villar-PiquéRaimon Sabate
Dec 12, 2012·Acta Biomaterialia·Olivia Cano-GarridoElena García-Fruitós
Apr 14, 2016·Chemistry : a European Journal·Ana B CaballeroPatrick Gamez
May 17, 2014·Prion·Raimon Sabate
Aug 16, 2016·Frontiers in Microbiology·Salvador Ventura
Feb 13, 2018·Molecular Neurobiology·Anna Villar-PiquéInga Zerr
Mar 30, 2019·Current Protein & Peptide Science·Ana B CaballeroRaimon Sabate

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Methods Mentioned

BETA
fluorescence spectroscopy
Infrared Spectroscopy

Software Mentioned

OPUS MIR Tensor

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