Brain Canada Brain Canada
FR Donate

Defining the mechanism of inhibition of tau aggregation by the molecular chaperone, DNAJA2

Principal Investigator:
  • Sue-Ann Mok, University of Alberta

Project Overview

Alzheimer’s Disease is a progressive and fatal disease that currently afflicts up to 400,000 Canadians over the age of 65. One key observation about this disease is that there is an abnormal “clumping” (aggregation) of specific proteins such as tau. Proteins normally need to keep a certain shape to perform their functions in the cell. Aggregation irreversibly destroys the function of these proteins and may promote negative consequences with regards to the affected cell’s health. Our cells have a large defense system of proteins called chaperones that can recognize incorrectly shaped or aggregating proteins. These chaperones can assist in refolding defective proteins or clearing them from the cell. We have identified a particular chaperone, DNAJA2, that can prevent the aggregation of tau. Moreover, DNAJA2 is found in high levels in the damaged neurons of samples from patients with Alzheimer’s as well as in patients with a higher risk of developing Alzheimer’s. We hypothesize that DNAJA2 may be triggered in patient neurons to surround the aggregates and prevent them from causing more damage. We will perform experiments to see if forcing cells to make more DNAJA2 prevents tau aggregates from hopping into neighbouring cells where they can cause new rounds of aggregation and damage. We will also carry out experiments to see if there are factors in neurons called microRNAs that block DNAJA2 from being made as the disease gets worse, speeding up cell damage and death. Our project will provide an in-depth look at how naturally protective proteins in our cells, such as DNAJA2, might be harnessed as a way to fight Alzheimer’s disease.