2021 Alzheimer's Association Research Grant (AARG)

Investigation of a Novel Alzheimer's Disease-Related Microprotein

How may microproteins impact the biological brain changes associated with Alzheimer’s?

Ryan Boudreau, Ph.D.
University of Iowa
Iowa City, IA - United States

Background

Each cell in the human body has a highly specific machinery to make proteins and instruction for each biological function. In order to make a protein, a specific gene within the DNA (the genetic instructions) is turned “on” and the cell’s machinery makes a small piece of genetic material, called ribonucleic acid (RNA). While some RNA molecules code for the creation of the protein, others, known as noncoding RNA, have other functions.  

Recently studies suggest some of the noncoding RNAs encode tiny microproteins. Certain types of noncoding RNAs appear to play a role in diseases including Alzheimer’s and other dementias. Studies have identified several microproteins encoded by these noncoding RNAs, but their role in the biology remains unknown. 

Previously, Dr. Ryan Boudreau and colleagues identified a particular microprotein called NC1314 that is lower in the brains of older individuals and even more decreased in the brains of individuals who had Alzheimer’s. Dr. Boudreau believes that NC1314 may help regulate the production of another protein, beta-amyloid in the brain. Beta-amyloid accumulates in Alzheimer’s to form plaques, a hallmark brain change observed in Alzheimer’s.
 

Research Plan

The research team will investigate how the microprotein NC1314 may impact the transport of the beta-amyloid within and out of the in brain cells. The researchers will evaluate the impact of NC1314 in cells grown in laboratory dishes and in the brains of genetically engineered Alzheimer’s-like mice and cognitively unimpaired mice. In addition, Dr. Boudreau and colleagues will study another microprotein known as CTXN3 that may be closely related to NC1314 for its impact in the model system as well.

Impact

If successful, the results of this project may shed light on new biological underpinning that occur in Alzheimer’s and may identify potential new therapeutic avenues for the treatment of Alzheimer’s and other dementias.