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2015 Grants - Zheng
Design of Peptide-Nanoparticle Conjugates as Abeta Inhibitors
Jie Zheng, Ph.D.
The University of Akron
2015 New Investigator Research Grant
Can a new class of peptide-based inhibitors be developed as a potential treatment to prevent beta-amyloid accumulation in Alzheimer’s disease?
The protein fragment beta-amyloid (also known as Abeta) is thought to contribute to dysfunction and loss of nerve cells in Alzheimer’s disease. Beta-amyloid molecules are produced in the healthy brain, but in Alzheimer’s they tend to become structurally abnormal leading to “misfolded” forms that can accumulate and have toxic effects on nerve cells.
To prevent amyloid toxicity, researchers have tried to design molecules that bind to misfolded beta-amyloid and hinder its accumulation in the brain, while leaving normal beta-amyloid intact to continue its necessary functions. Many of these “peptide-based inhibitors,” however, break down too easily in the body or are ineffective at crossing the blood-brain barrier, the layer of cells that protects the brain from molecules in the blood. These limitations have kept this type of drug from being effective in the brain.
For their current grant, Jie Zheng, Ph.D., and colleagues plan to develop an improved class of peptide-based inhibitors that could potentially be tested as a treatment for Alzheimer’s disease. These compounds will be designed so that they bind more effectively to misfolded beta-amyloid molecules than earlier versions. The researchers will then combine the compounds with nanoparticles, or tiny molecular carriers, to help cross the blood-brain barrier effectively and to be less susceptible to degradation in the body. As part of this project, Dr. Zheng’s team will conduct a thorough assessment of how these novel compounds interact with beta-amyloid at a molecular level.
Dr. Zheng’s efforts could shed new light on how peptide-based inhibitors interact with beta-amyloid. This work could lead to the future development of novel therapeutics to stop amyloid production and help prevent or slow the progression of Alzheimer’s disease.