2021 Alzheimer's Association Research Fellowship (AARF)

RNA-Binding Proteins Musashi and Tau Strains in Alzheimer’s disease

How does the tau protein interact with other proteins in the brain in Alzheimer’s?

Mauro Montalbano, Ph.D.
University of Texas Medical Branch at Galveston
Galveston, TX - United States

Background

Beta-amyloid and tau accumulate in the brain to form plaques and tangles respectively, two of the hallmark brain changes observed in Alzheimer’s. Tau is normally modified by the addition of a molecule known as phosphate to specific parts of the tau protein. In Alzheimer’s and other brain diseases, tau has too many of these modifications, leading to tau clumping together to form the tangles. These tangles contribute to brain cell damage in Alzheimer’s and other dementia.

Dr. Mauro Montalbano and his colleagues recently found that in Alzheimer’s, tau protein interacts with a family of proteins called Musashi (MSI). However, the biological mechanisms that underlie this interaction, and its impact on disease progression, are unknown.
 

Research Plan

Dr. Montalbano and his team will study the pattern of how tau and MSI interact in Alzheimer’s. Using advanced microscopic techniques, the researchers will characterize different shapes of the tau protein and their associations with MSI in the brains of individuals who had Alzheimer’s. In addition, Dr. Montalbano and research team will study the impacts of tau-MSI interactions on brain cell health and survival in cells grown in laboratory dishes and in the brains of genetically engineered Alzheimer’s-like mice to better understand this interaction and how it may contribute to disease-related changes. 
 

Impact

The findings may contribute to our understanding of the role of tau tangles in the onset and progression of Alzheimer’s. The results may suggest new therapeutic targets and new biological pathways relevant to the disease.