Oleuropein aglycone prevents cytotoxic amyloid aggregation of human amylin.

In this study Rigacci and her research team investigated the effects on amylin aggregation and cytotoxicity of the Secoiridoid oleuropein aglycone. Pancreatic amyloid deposits of amylin are a hallmark of Type II diabetes and considerable evidence indicates that amylin oligomers are cytotoxic to beta-cells. Oleuropein aglycone is a naturally occurring molecules, that could be able to hinder amylin aggregation or to protect cells against aggregate cytotoxicity.


The authors found that oleuropein aglycone, when present during the aggregation of amylin, consistently prevented its cytotoxicity to RIN-5F pancreatic beta-cells. A lack of interaction with the cell membrane of amylin aggregates grown in the presence of oleuropein was shown by fluorescence microscopy and synthetic lipid vesicle permeabilization. Moreover, our ThT assay, circular dichroism analysis and electron microscopy images suggested that oleuropein interferes with amylin aggregation, resulting in a different path skipping the formation of toxic pre-fibrillar aggregates.
 
These results provide data for the possible pharmacological use of oleuropein aglycone to prevent or to slow down the progression of type II diabetes.



Fig. 2. (A) Cells treated with hIAPP. (B) Cells treated with hIAPP incubated with oleuropein. (C) Control, untreated cells. (D) Cells treated with hIAPP that was aged without oleuropein and given to cells together with oleuropein.


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