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Epigallocatechin gallate (EGCG) reduces the intensity of pancreatic amyloid fibrils in human islet amyloid polypeptide (hIAPP) transgenic mice

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Item Type:Article
Title:Epigallocatechin gallate (EGCG) reduces the intensity of pancreatic amyloid fibrils in human islet amyloid polypeptide (hIAPP) transgenic mice
Creators Name:Franko, A., Rodriguez Camargo, D.C., Böddrich, A., Garg, D., Rodriguez Camargo, A., Rathkolb, B., Janik, D., Aichler, M., Feuchtinger, A., Neff, F., Fuchs, H., Wanker, E.E., Reif, B., Häring, H.U., Peter, A. and Hrabě de Angelis, M.
Abstract:The formation of amyloid fibrils by human islet amyloid polypeptide protein (hIAPP) has been implicated in pancreas dysfunction and diabetes. However, efficient treatment options to reduce amyloid fibrils in vivo are still lacking. Therefore, we tested the effect of epigallocatechin gallate (EGCG) on fibril formation in vitro and in vivo. To determine the binding of hIAPP and EGCG, in vitro interaction studies were performed. To inhibit amyloid plaque formation in vivo, homozygous (tg/tg), hemizygous (wt/tg), and control mice (wt/wt) were treated with EGCG. EGCG bound to hIAPP in vitro and induced formation of amorphous aggregates instead of amyloid fibrils. Amyloid fibrils were detected in the pancreatic islets of tg/tg mice, which was associated with disrupted islet structure and diabetes. Although pancreatic amyloid fibrils could be detected in wt/tg mice, these animals were non-diabetic. EGCG application decreased amyloid fibril intensity in wt/tg mice, however it was ineffective in tg/tg animals. Our data indicate that EGCG inhibits amyloid fibril formation in vitro and reduces fibril intensity in non-diabetic wt/tg mice. These results demonstrate a possible in vivo effectiveness of EGCG on amyloid formation and suggest an early therapeutical application.
Keywords:Amyloid, Amyloidosis, Biomarkers, Catechin, Islet Amyloid Polypeptide, Molecular Conformation, Molecular Models, Neuroprotective Agents, Pancreas, Protein Binding, Transgenic Mice, Animals, Mice
Source:Scientific Reports
ISSN:2045-2322
Publisher:Nature Publishing Group
Volume:8
Number:1
Page Range:1116
Date:18 January 2018
Official Publication:https://doi.org/10.1038/s41598-017-18807-8
PubMed:View item in PubMed

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