IAPP Aggregation and Cellular Toxicity are Inhibited by PGG
Authors:
Pei-Yu Kao, Catalina Pereira Pereira, Karla Roman, Marisa TakiguchiMentors:
- David Moffet, Associate professor of chemistry and biochemistry, Loyola Marymount University
- Luiza Nogaj, Assistant Professor of Biology, Mount St. Mary's College
The molecule 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG) has previously shown to possess positive pharmacologic activities that of which include anti-cancer and anti-diabetic. There is very little knowledge about the mechanism of action of PGG that results in these positive pharmacological activities. We show in this study that PGG is a strong inhibitor of IAPP (Islet Amyloid Polypeptide, Amylin) aggregation. Preventing the initial aggregation of IAPP is a strategy amongst others that can slow down the progression of Type II diabetes, and possibly prevent the disease from occurring. Equal molar ratios of PGG to IAPP substantially reduced the ability of IAPP to bind to thioflavin T. Atomic force microscopy showed that PGG prevented amyloid-based fiber formation under rigorous conditions conducive to forming IAPP aggregates. PGG was also found to protect PC12 rat cells from toxic IAPP. Known inhibitors of IAPP, tannic and gallic acid (structure relatives) were both compared to PGG. In every test, PGG was far superior to tannic and gallic acid at inhibiting IAPP aggregation. These results suggest that PGG is a potent inhibitor of IAPP amyloid aggregation and also that it may be a potential lead molecule for the development of an amyloid inhibiting therapeutic drug.