Development of Inhibitors of the Tau-Fyn Interaction for the Treatment of Alzheimer's Disease

The purpose of this project is to identify a novel therapy for treating Alzheimer’s disease (AD). We are investigating compounds that would stop the interaction between two proteins, tau and Fyn. Considerable data indicates that blocking this interaction could ameliorate AD.

Tau is widely considered an excellent target for AD, but it is unclear how to target it. Normal tau serves a physiologic role in humans, including to stabilize microtubule structures that are important for transporting molecules throughout the neuron. However, while we know that tau is involved in Alzheimer’s disease, we don’t yet know exactly how tau contributes. A variety of data indicate that Tau’s interaction with another protein known as Fyn tyrosine kinase may be critical. Tau and Fyn bind with each other, and we and others have obtained a variety of data indicating that Fyn is involved in AD.  We are investigating compounds that would stop the interaction between tau and Fyn.  We set out to develop inhibitors of the tau-Fyn interaction and screened approximately 100,000 compounds to identify several “hits” that block the interaction. The next phase of the project is to further evaluate and refine these hits to develop lead compounds for evaluation in animal models. If successful, this work could help identify a new therapeutic approach to AD.