Using a new approach to view structures generated in a disease called fibrils, the researchers were able to explain the overall rope-like structure of the fibrils formed by proteins in type 2 diabetes, as well as the mechanism by which the structures form. This is important information for researchers working to develop therapies to attack type 2 diabetes and other neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and Huntington’s disease.
“If we can understand what makes these proteins go bad and what they look like, we can develop drugs to treat type 2 diabetes and other related diseases,” said Ralf Langen, professor of biochemistry and molecular biology at the Keck School and corresponding author of the study.
Langen’s research group collected the key data on the fibrils using an electron paramagnetic resonance (EPR) technique that takes advantage of “spin labels” placed in key places on the protein. These results then were used to generate the fibril structures through computational methods.
Ian Haworth, associate professor at the School of Pharmacy and lead researcher in the computational work, said, “It’s a great example of using basic science methodology to address health-related problems and promote translational research.”
The research was published online as a Paper of the Week in The Journal of Biological Chemistry.
The fibrils are contained in proteins that change shape, clump together and deposit in affected areas of the body in patients suffering from type 2 diabetes, Alzheimer’s disease, Parkinson’s disease and Huntington’s disease.
To get a higher-resolution view of the fibrils formed in type 2 diabetes, the researchers developed an approach combining site-directed spin labeling with continuous wave and pulsed EPR, as well as computational refinement.
Type 2 diabetes, also known as adult-onset diabetes, is the most common form of diabetes. Patients with this chronic condition do not produce enough insulin or certain cells do not respond to insulin (also known as insulin resistance). The result is high levels of glucose in the blood. The disease can be attributed to family history and genes, but patients also may be overweight.
Sahar Bedrood was lead author of the study. Contributing researchers included Yiyu Li (School of Pharmacy), Jose Mario Isas, Balachandra G. Hegde, Ulrich Baxa (National Institutes of Health) and Haworth.
This study was funded by the National Institutes of Health.
The University of Southern California