Targeting the Tau-Fyn Interaction in Alzheimer’s Disease

2016  -  Birmingham, AL, USA

Grantees

Dr. Travis Rush

Organizations

University of Alabama at Birmingham

Supervising Advisor: Dr. Erik Roberson

Project summary:

Alzheimer’s disease (AD) affects more than 5 million Americans and is expected to affect 13 million by 2050. Current treatments provide very little benefit, and the disappointing results of clinical trials targeting the amyloid protein pathology characteristic of AD underscore the urgent need for new treatment strategies. Another protein, tau, is widely considered an excellent therapeutic target for treating AD, as tau is required for amyloid-beta (Aβ) driven neuronal death and dysfunction. Further, genetically removing tau from mice dramatically protects against the behavioral and pathological abnormalities in a model of AD. However, targeting tau in humans has remained a significant challenge to the biomedical field.

Several observations have raised our interest in the interaction between tau and another protein, fyn. To briefly summarize, tau abnormalities cause fyn to mislocalize within neurons, which leads to hyperexcitability and memory deficits. These dysfunctions are prevented by tau reduction, and there is mounting evidence that they are mediated by the tau-fyn interaction. Our ongoing studies represent a drug discovery effort to identify and deliver effective inhibitors of the tau-fyn interaction. Specifically, we will complete an examination of the dozens of compounds we know to inhibit the interaction of purified tau and fyn to determine whether they prevent AD-related neuronal death and dysfunction. We will also be verifying that these inhibitors block the tau-fyn interaction in neurons and brain tissue. Once we have identified the best candidates, we will move forward with pre-clinical trials in AD model mice.

This project is a continuation from the Advisor Fellowships 2015 program | View 2015 project details