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Tuesday, June 26, 2018
Researchers discover insights into amyloids associated with Alzheimer's and type 2 diabetes
Using the Virginia Tech HyperCube immersive environment, Justin Lemkul (left) and Anne Brown (right) examine the structure of amyloid β-peptide associated with Alzheimer’s disease.
A Virginia Tech research team has discovered insights into the stabilizing forces of amyloid fibrils that are associated with Alzheimer's disease and type 2 diabetes.
These findings were recently published in the Journal of Molecular Biology.
Amyloids are aggregates of proteins that form a shape that allows many copies of that protein to stick together to form fibrils. The accumulation of amyloid fibrils in the brain contributes to Alzheimer's disease, and the accumulation of amyloid fibrils in the pancreas contributes to type 2 diabetes by damaging cells that produce insulin.
Justin Lemkul, an assistant professor of biochemistry in the College of Agriculture and Life Sciences, and his team's research focuses on applying computer simulations to understand mechanisms of protein aggregation that are difficult or even impossible to recreate in a laboratory setting.
Elucidating the structure and stability of these amyloid fibrils is important for developing future anti-amyloid drug therapies.
For this research, Lemkul's team performed the first-ever simulations of amyloid fibrils using a physical model that included electronic polarization to understand the forces stabilizing three amyloid-forming proteins observed in Alzheimer patients: microtubule-associated protein tau, amyloid β-peptide, and islet amyloid polypeptide (IAPP). IAPP is also associated with amyloid fibrils in type 2 diabetes patients.
"We found that several amino acids in these three amyloid-forming proteins are particularly sensitive to small changes in their environment, particularly glycine, which plays a major role in stabilizing amyloid aggregates," said Lemkul, an affiliate of the Fralin Life Science Institute and Virginia Tech Center for Drug Discovery.
Anne Brown, an assistant professor in research and informatics, University Libraries, is a contributing author and performed the IAPP simulations and analysis for the paper.
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