Lowering Tau in the Brain

Jason E Gestwicki, PhD
University of California, San Diego (San Diego, CA, United States)
Year Awarded:
Grant Duration:
July 1, 2012 to September 30, 2014
Award Amount:
Grant Reference ID:
Award Type:
Award Region:
US Southwestern

Co-principal Investigators

Chad A Dickey, PhD
University of South Florida (Tampa, FL, United States)

Chemical Approaches to Reducing Tau Levels


Tau is a protein that aberrantly accumulates in the brains of patients with Alzheimer's disease. The goal of this proposal by Drs. Jason E. Gestwicki, Chad Dickey, and colleagues is to determine whether newly discovered chemical inhibitors of heat shock protein 70 (Hsp70) will reduce tau accumulation. Such compounds are expected to be potential therapeutics with an under-explored mechanism.


The goal of this project is to test whether heat shock protein 70 (Hsp70) might be a new, under-explored drug target for Alzheimer's disease (AD). Hsp70 has been linked to AD because it is able to counteract the accumulation of a protein, tau, which is commonly observed in AD patients. However, no drug-like chemicals have been available that bind to Hsp70, so it hasn't been clear whether it could be a new therapeutic target.

Dr. Jason E. Gestwicki and his team recently uncovered a promising class of Hsp70-binding compounds and have shown that these compounds reduce tau accumulation in cellular and animal models of AD. The next major goal is to improve the safety and efficacy of these compounds before they are tested in human clinical trials.

These studies are designed to establish whether Hsp70 is a bona fide drug target for AD. The goal of this project is to produce a set of pre-clinical data that could, if successful, provide the rationale for advancing these compounds towards clinical trials.

About the Researcher

As of April 1, 2013, Dr. Gestwicki is the Associate Professor in the In Residence series at the Institute for Neurodegenerative Diseases (IND) and the Department of Pharmaceutical Chemistry at UCSF (formerly the William B. Pratt Collegiate Professor of the Life Sciences Institute and Associate Professor of Pathology and Biological Chemistry at the University of Michigan). He completed doctoral studies at University of Wisconsin and post-doctoral work at Stanford University. Dr. Gestwicki's laboratory uses the tools of organic chemistry to explore how molecular chaperones regulate protein misfolding and accumulation in neurodegenerative disorders. In addition to a BrightFocus award, Dr. Gestwicki has been funded by the National Institutes of Health and the National Science Foundation.

Dr. Gestwicki is originally from western New York State and completed undergraduate studies in chemistry at the State University of New York College at Fredonia. He started his independent research group at the University of Michigan in 2005 and is focused on finding new ways of treating Alzheimer's disease.