Burris and Griffett Publish Breakthrough Research on Alzheimer’s Disease and Brain Cancer
Published on 16 November 2020
Tom Burris, Ph.D., Alumni Chair in Pharmaceutical Education and vice president for research and graduate education at University of Health Sciences and Pharmacy in St. Louis and Kristine Griffett, Ph.D. assistant professor of pharmacology, have spent several years on an independent research project studying a nuclear receptor that is connected to both Alzheimer’s disease and glioblastoma, an aggressive form of brain cancer.
The research team, which also included Lamees Hegazy, Ph.D., assistant professor of medicinal chemistry, has developed a method for targeting a receptor, known as TLX, which could lead to breakthrough treatments for both conditions. The team’s research on TLX was recently published in Cell Chemical Biology.
“TLX is a nuclear receptor involved in cellular proliferation in the brain as well as neuronal stem cells,” Burris explained. “For our research, we’re focusing on the receptor’s involvement in neurogenesis, which is the process by which new neurons are formed in the brain. In Alzheimer’s disease, we would like to stimulate the brain to make additional neuronal cells in a part of the brain that is involved in memory and TLX appears to be important in that process. However, TLX appears to get ‘taken over’ in glioblastomas, where it is used to help that type of brain cancer proliferate. Studying the TLX receptor and how to modulate its activity could be very important for targeted treatments for these diseases.”
Nuclear receptors are like complex computer programs that can be switched on or off to either start or stop a certain cellular activity, such as cell proliferation. The switching is done by ligands, which are compounds that interact with the receptor and activate or deactivate its various functions. For scientists to be able to manipulate a receptor to treat a disease or condition, they have to identify which ligands recognize the receptor and bind to it, and determine if they start or stop these programs and how they affect the body.
When a receptor has been identified but its ligands are still unknown, it’s called an orphan receptor. Burris is especially interested in orphan receptors like TLX because they are an untapped mine of potential for creating innovative treatments for a number of serious diseases and conditions.
For this project, it has taken Burris’ team several years to identify the ligands connected to TLX.
“The breakthrough that we’ve made is to identify retinoids as the ligands for TLX,” Burris explained. “Retinoids are naturally occurring compounds in the vitamin A family, but they have potential side effects. Our research has demonstrated that synthetic retinoids could be developed to precisely target TLX’s activities to treat specific diseases or conditions without the side effects associated with natural retinoids.”
Burris’ team has discovered that activating the TLX receptor can produce more neurons, which could be used to treat Alzheimer’s disease and other forms of dementia, while deactivating TLX can slow glioblastoma growth. The complex role that TLX plays in maintaining brain health needs to be studied further before therapeutics for either of these diseases can be developed. Burris’ hope is that his work will reach other scientists who can use the discoveries to develop new treatments for these and other conditions.
“Publication is a crucial step in moving our research forward, and we are delighted that Cell Chemical Biology accepted our paper,” Burris explained. “We are excited to share our discoveries with our peers so that this research can eventually lead to real treatments that help people. Publishing with a well-respected, widely-read journal gives our work the credibility and recognition needed to move forward with this exciting research.”