Journal article
Inhibition of hIAPP Amyloid Aggregation and Pancreatic β-Cell Toxicity by OH-Terminated PAMAM Dendrimer
EN Gurzov, B Wang, EH Pilkington, P Chen, A Kakinen, WJ Stanley, SA Litwak, EG Hanssen, TP Davis, F Ding, PC Ke
Small | Published : 2016
Abstract
Human islet amyloid polypeptide (hIAPP, or amylin) forms amyloid deposits in the islets of Langerhans, a phenomenon that is associated with type-2 diabetes impacting millions of people worldwide. Accordingly, strategies against hIAPP aggregation are essential for the prevention and eventual treatment of the disease. Here, it is shown that generation-3 OH-terminated poly(amidoamine) dendrimer, a polymeric nanoparticle, can effectively halt the aggregation of hIAPP and shut down hIAPP toxicity in pancreatic MIN6 and NIT-1 cells as well as in mouse islets. This finding is supported by high-throughput dynamic light scattering experiment and thioflavin T assay, where the rapid evolution of hIAPP ..
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Awarded by National Institute of Environmental Health Sciences
Funding Acknowledgements
E.N.G. and B.W. contributed equally to this work. This work was supported by ARC Project No. CE140100036 (T.P.D.), NSF CBET-1232724 (P.C.K. and F.D.), NIH R15ES022766-01A1 (F.D.), and NHMRC Project Grant APP1071350 (E.N.G.). T.P.D. is thankful for the award of an Australian Laureate Fellowship from the ARC. E.N.G. was supported by a Juvenile Diabetes Research Foundation (JDRF) fellowship. The St Vincent's Institute receives support from the Operational Infrastructure Support Scheme of the Government of Victoria. The authors acknowledge Dr. Shane Seabrook for assistance with the DLS measurement. All simulations were performed on the Palmetto high performance cluster at Clemson University CCIT.