2015-2016 Alzheimer’s and Related Diseases Research Award*

Molecular Mechanisms of Amylin as a Novel Contributor to Alzheimer’s Disease

VCoA*The Virginia Center on Aging which administers the Alzheimer’s and Related Diseases Research Award Fund for the Commonwealth of Virginia, provides seed money to researchers in Virginia to stimulate innovative research into biomedical and psychosocial aspects of dementia, including cell biology, caregiving, and animal modeling.


Molecular Mechanisms of Amylin as a Novel Contributor to Alzheimer’s Disease

Bin Xu, PhD, David Bevan, PhD and Ling Wu, MD, PhD

Virginia Tech, Shenandoah University

Epidemiological studies have shown a link between type 2 diabetes (T2D) and the risk for AD. A feature com-mon to both diseases is the formation of amyloid peptide aggregates. The peptide associated with AD is amyloid beta (Aβ), and for T2D, it is amylin. Amylin can possibly travel to the brain, and aggregate themselves into amylin amyloids, or combine with Aβ, to form amylin/Aβ-crossed amyloids. This project applied an interdiscipli-nary approach involving cellular, biochemical, biophysical, and computational methods to define the amylin amy-loid species, establish cell-based neurotoxicity assays, and assess amylin/Aβ-crossed amyloid formation and toxi-city. The investigators were able to define three amylin amyloid species that have distinct sizes and shapes. They further defined how amylin forms amyloid and fibril using multiple biochemical and biophysical methods. They established cell-based functional assays that can be used to assess amylin-induced neurotoxicity. Two compounds used in Alternative and Complementary Medicine to treat diabetes, inflammation and neuroprotection were found to potently inhibit amylin-induced neurotoxicity. Mechanistic insights were provided through detailed and com-prehensive cellular, biochemical, and computational simulation studies. These results serve as the basis for a future comprehensive research program to elucidate molecular events that contribute to AD as well as to devise potential treatment strategies.

(Dr. Xu may be contacted at 540/231-1449, binxu@vt.edu; Dr. Bevan may be contacted at 540/231-5040, drbevan@vt.edu; Dr. Wu may be contacted at 540/231-8442, wul3@vt.edu)

 

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More 2015-2016 Funded Projects