Amyloid peptide channels: blockade by zinc and inhibition by Congo red (amyloid channel block)

Amyloid peptides are the major constituents of amyloid deposits in various amyloid diseases including Alzheimer's disease, type II diabetes mellitus, prion diseases and others. The hallmark of amyloid is the binding of the dy e, Congo red, which creates characteristic staining doe to the dye's abilit y to bind the beta sheet aggregates referred to as amyloid. Previous report s have demonstrated that several cytotoxic, amyloidogenic peptides can form ion channels in planar phospholipid bilayer membranes and have suggested t hat these channels may represent the pathogenic mechanism of cell and tissu e destruction in amyloid disease. Furthermore, zinc and Congo red can ameli orate or prevent the pathogenic effect of certain amyloid peptides. We repo rt here that zinc at micromolar concentrations caused a reversible blockade of islet amyloid polypeptide (IAPP, amylin) and PrP 106-126 channels where as calcium and magnesium did not. Congo red completely inhibited channel fo rmation if preincubated with amyloid peptides, but had no effect on IAPP or PrP 106-126 channels once formed These results suggest a requirement for a ggregation for the formation of amyloid peptide channels and are consistent with the "channel hypothesis" of amyloid disease. They also suggest potent ial avenues for ameliorative therapy of these illnesses.