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. 2019 Mar;26(1):24-33.
doi: 10.1080/13506129.2019.1568978. Epub 2019 Feb 9.

Cell assay for the identification of amyloid inhibitors in systemic AA amyloidosis

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Cell assay for the identification of amyloid inhibitors in systemic AA amyloidosis

Ioana Puscalau-Girtu et al. Amyloid. 2019 Mar.

Abstract

Systemic AA amyloidosis is still, up to this day, a life-threatening complication of chronic inflammatory diseases. Despite the success of anti-inflammatory treatment, the prognosis of some AA patients is still poor, which is why therapies directed at the amyloidogenic pathway in AA amyloidosis are being sought after. The cell culture model of amyloid formation from serum amyloid A1 (SAA1) protein remodels crucial features of AA amyloid deposit formation in vivo. We here demonstrate how the cell model can be utilized for the identification of compounds with amyloid inhibitory activity. Out of five compounds previously reported to inhibit self-assembly of various amyloidogenic proteins, we found that epigallocatechin gallate (EGCG) inhibited the formation of SAA1-derived fibrils in cell culture. From a series of compounds targeting the protein quality control machinery, the autophagy inhibitor wortmannin reduced amyloid formation, while the other tested compounds did not lead to a substantial reduction of the amyloid load. These data suggest that amyloid formation can be targeted not only via the protein self-assembly pathway directly, but also by treatment with compounds that impact the cellular protein machinery.

Keywords: AA amyloidosis; Amyloid quantification; anti-amyloid; macrophage; thioflavin T.

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