Synergistic action of polyanionic and non-polar cofactors in fibrillation of human islet amyloid polypeptide

Abstract 

Recent studies have led us to suppose that synergistic action of multiple solute cofactors could play substantial roles in amyloid-type fibrillogenesis of pathogenic polypeptides. To support this view, we performed aggregation experiments of human islet amyloid polypeptide (IAPP) in media containing both polyanions and non-polar solvents. The results demonstrated that the fibrillation at sub-micromolar IAPP occurred only when polyanionic and non-polar solutes coexist. A simple sum of two independent cofactor’s effects could not account for the synergistic action. We propose that this synergy of polyanionic and nonpolar milieus could substantially modify the amyloidgenesis in the human body.

Abbreviations: IAPP, human islet amyloid polypeptide, ThT, thioflavin T, HFIP, 1,1,1,3,3,3-hexafluoroisopropanol, TFE, 2,2,2-trifluoroethano, iPrOH, isopronanol, EtOH, ethanol, polyE, poly-l-glutamate, TEM, transmission electron microscopy, GAG, glycosaminoglycan

Keywords: IAPP, Amyloid, Fibrillation, Alcohol, Polyanion, Synergistic effect