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Research Grants 2011

To view an abstract, select an author from the vertical list on the left.

2011 Grants - Mantha

APE1/Ref-1's Dual Functions Countering Beta-Amyloid Induced Genotoxicity

Anil K. Mantha, Ph.D.
The University of Texas Medical Branch at Galveston
Galveston, Texas

2011 New Investigator Research Grant

The protein fragment beta-amyloid has been shown to induce the activity of reactive oxygen species (ROS) in Alzheimer's disease. These highly reactive chemicals are believed to cause damage to the structure of brain cells and to inhibit cellular function. Such damage may be directed at the cells' DNA. DNA is a component of cells that contains the specific genetic information needed for any living organism to develop and function. One mechanism that the brain uses to repair DNA damage involves the protein called abasic endonuclease (APE1/Ref-1). This protein also plays a role in gene transcription, or the process by which a gene is "activated" so that it is converted into a protein. However, the potential role of APE1/Ref-1 in preventing amyloid-related DNA damage is poorly understood.

In preliminary studies using rat brain cells, Anil Kumar Mantha, Ph.D., and colleagues have found that beta-amyloid appeared to disrupt the activities of APE1/Ref-1 and make the cells more vulnerable to amyloid-related toxicity. They also found that by overexpressing APE1/Ref-1 in cells, they could decrease levels of amyloid-induced ROS — thus reducing levels of oxidative damage. Both these results suggest a strong connection between beta-amyloid and the APE1/Ref-1 repair mechanism.

For this study, Dr. Mantha and colleagues will conduct more extensive research with cultured brain cells to verify this beta-amyloid/APE1 connection. They also expect to obtain a better understanding of the mechanisms underlying the connection. Such work could help clarify how beta-amyloid exerts its toxicity in Alzheimer's disease. It could also lead to more precise therapeutic strategies for people suffering with dementia.

Alzheimer's Association International Conference | July 16-20, 2017, London, England

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