In the presence of unusually high levels of these enzymes, some proteins tend to form denser clusters than normal in vivo. If the aggregates grow in size, it can lead to a build-up of insoluble plaques that can block neurovascular transport and cause neural cell death.
"If higher TGase concentrations in cerebrospinal fluid and in the brain lead to protein agglomeration, then their inhibition could reduce symptoms, delay the onset of agglomeration, and maintain viable neural cell health extending the quality of life for those afflicted," hypothesizes Brian Love, a professor of materials science and engineering (MSE) at Virginia Tech.
Love, who focuses his research on tissue and cell engineering, and Elena Fernandez Burguera, a post-doctoral research associate, are evaluating specific therapies to fight the abnormally high TGase binding. Based upon the prior work of several others who are conducting clinical trials, Love and Burguera are developing an in vitro model to evaluate the ability of several inhibitors to block protein aggregation by TGases.
Again, based on the work of other scientists, "several compounds show some positive effects," Love says. These include creatine, cystamine hydrochloride, and a few others. "The development of an inhibition protocol may help test the efficacy of other inhibitors as well," the engineer adds.
The Virginia Tech researchers are looking at the enzymatic binding of protein-bound polystyrene particles as models. Groups of particles are dispersed in calcium-rich aqueous solutions containing TGases. Once mixed, the particle binding begin
Contact: Lynn Nystrom