Alzheimer’s disease (AD) is one of the most devastating neurodegenerative conditions, afflicting more than 4 million Americans each year. The available FDA-approved drugs only stabilize the conditions. More robust medications are needed to improve the syndrome. Synaptic damage is the earliest sign of AD, which leads to memory loss. Therefore, uncovering novel synaptic mechanisms and identifiable targets for the disease is key for developing effective treatments. With new funding, Francesca-Fang Liao, PhD, and her research team plan to do just that.
Dr. Liao, who is an associate professor in the Department of Pharmacology, College of Medicine at the University of Tennessee Health Science Center (UTHSC), has received a grant totaling $1.4 million from the National Institute on Aging, a subsidiary of the National Institutes of Health. The award will be used to support a project titled, “Is HSF1 The Key in Mediating HSP90 Inhibitor Effect in AD?” The award will be distributed over five years.
Dr. Liao and her research team recently discovered that a pharmacological inhibitor of HSP90 can powerfully stimulate multiple genes important for synaptic functions and prevent memory loss in symptomatic Alzheimer’s mouse models. So far, the interest for developing a feasible HSP90 inhibitor for AD therapy is high, however, brain penetration and systemic toxicity present major challenges for development.
Previous efforts have shown feasibility in rodent models. Researchers have also discovered an activated transcription factor named HSF1, a universal master switch in stress response, likely being a major player in brain functions. Full evaluation on the efficiency and safety of this brain penetrating inhibitor is extremely important. If successful, it could lead to further development of this strategy toward clinical trials in AD patients.
“We are excited to study HSF1 for its potential important roles in synaptic performance and perhaps in other brain functions in the near future,” said Dr. Liao. “We were hugely surprised to learn that very little research has been conducted in regards to this important molecule.”