Dihydropyrimidine-thiones and clioquinol synergize to target b-amyloid cellular pathologies through a metal-dependent mechanism

DHPM-thiones rescue Ab-mediated toxicity in a metal-dependent manner that strongly synergizes with clioquinol, a known metal-binding and cytoprotective compound. RNA-seq experiments reveal a modest, yet specific effect on metal-responsive genes that do not change with the inactive control compound. Overall design: Treatment of biological replicates with DMSO, 0.8 uM clioquinol, or 20 uM 10{3,3,1} (DHPM-thione) for ~6 hours prior to harvesting of cells and isolation of total RNA.

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Tardiff DF, Brown LE, Yan X, Trilles R, Jui NT, Barrasa MI, Caldwell KA, Caldwell GA, Schaus SE, Lindquist S