Sulfur Metabolism Imbalance in Alzheimer’s Disease Is Focus of New Research

University of Texas at Arlington (UTA) researchers will study the catalytic processes of sulfur-oxidizing enzymes, especially the chemical mechanism of a key enzyme, cysteine dioxygenase. Their work could lead to new therapies for Alzheimer’s and autism, diseases in which sulfur metabolism is known to be disrupted.

Dr. Brad Pierce, a UTA assistant professor of biochemistry, is principal investigator for the study, supported by a three-year, $333,810 National Institutes of Health grant administered through its Academic Research Enhancement Award Program.

The project will build on previous research by Dr. Pierce and his team into the circumstances under which this enzyme produces reactive oxygen species, harmful molecules that damage cells and are linked to the pathogenesis of several diseases, including cancer, Parkinson’s disease, and arthritis.

In a paper published in 2013 in Biochemistry, the team described how mutations outside of the enzyme’s active site environment impact the release of reactive oxygen species. As a strategy for the new project, researchers will use rapid-mix, freeze-quench techniques to trap and analyze chemical reactions at extremely short-span intervals, comparing the processes both in mammals and bacteria. “Our work is to retro-engineer the sulfur oxidation process and map out the chemical mechanism of a key enzyme — cysteine dioxygenase — in both mammals and bacteria, to provide the necessary framework to develop effective therapies and drugs for these different disease states,” Dr. Pierce said in a press release.

Studying the enzyme’s behavior in bacteria also might bring new insights into treating “superbugs,” or bacterial strains resistant to antibiotics, by possibly revealing alternative routes to disrupting bacterial metabolism.

“Dr. Pierce’s research will provide the essential basic scientific background needed to develop therapies for critical conditions that are currently not understood. This work is at the heart of the positive impact that a modern, research university can have on society,” said Morteza Khaledi, dean of the UTA College of Science.