Background: The amyloidogenic peptides IAPP and ProIAPP1-48 are implicated in cell death in type 2 diabetes mellitus. While\r\nthe mechanism of their deposition in vivo is unknown we have shown that in vitro metals can both accelerate, for example Al(III),\r\nand inhibit, for example Cu(II), their formation of amyloid.\r\nMethods: We have used a combination of thioflavin T fluorescence (ThT) and transmission electron microscopy (TEM) to\r\ninvestigate the potency with which Cu(II) prevented human ProIAPP1-48 from forming sheets of amyloid fibrils both in the\r\nabsence and presence of significant molar excesses of Al(III) or Zn(II).\r\nResults: Cu(II) prevented ProIAPP1-48 from forming fibrillar materials with sheet structure at all concentrations above equimolar\r\nto peptide. At equimolar Cu(II) to ProIAPP1-48 fibrillar-like materials were observed by TEM though these were not ThT-positive.\r\nSignificant excesses of the competitive metals Al(III) and Zn(II) were unable to influence these effects of Cu(II).\r\nConclusions: Cu(II) was shown to be a potent inhibitor of amyloid formation by ProIAPP1-48 and its potency was unaffected by\r\nsignificant excesses of either Al(III) or Zn(II). If the propensities for IAPP and ProIAPP to form amyloid are central to the aetiology of\r\ncell death in type 2 diabetes mellitus then the availability of Cu(II) to prevent amyloidogenesis may be a critical factor for future\r\ntherapy.
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