2023 Alzheimer's Association Research Grant (AARG)

Therapeutic Potential of Lysine Crotonylation in Alzheimer's Disease

How does gene regulation impact memory and brain changes in Alzheimer’s?

Snehajyoti Chatterjee, Ph.D.
The University of Iowa
Iowa City, IA - United States

Background

A major focus of Alzheimer’s research is identifying genetics factors that may increase the risk of developing the disease. In addition to examining the specific genes that increase one’s risk, researchers are also studying ways in which genes are modified or activated in Alzheimer’s. Chemical modifications of histones, the proteins that wrap around DNA, help control whether genes are turned “on” or “off” in response to certain signals in the cell. One such modification is histone crotonylation – the process of attaching “crotonyl” groups to histones. Histone crotonylation has been shown to impact memory formation and could be associated with brain changes observed in Alzheimer’s.

Research Plan

Dr. Snehajyoti Chatterjee and colleagues will study the relationship between histone crotonylation and memory loss in Alzheimer’s. They will do this using genetically engineered Alzheimer’s-like mice that exhibit the same hallmark brain changes as individuals with Alzheimer’s. First, the researchers will use sophisticated gene sequencing techniques to identify genes that have been modified by histone crotonylation in the hippocampus, the specific region of the brain responsible for memory and learning. Next, Dr. Chatterjee and the team will increase histone crotonylation in these same mice and study their cognitive function to examine the therapeutic potential of histone crotonylation in Alzheimer’s. 

Impact

The study findings could provide insights into how gene activity could impact memory and brain changes observed in Alzheimer’s. If successful, the results could also give rise to new potential therapeutic targets to treat Alzheimer’s.