Inhibiting a Cell-Execution Protein

Inhibiting a Cell-Execution Protein

Apoptosis is a normal cellular process that enables damaged or defective cells to self-destruct—but uncontrolled apoptosis can be harmful.  For example, the death of heart-muscle tissue following heart attacks is largely due to apoptotic cell death. In a study published online on February 4 in Nature Chemical Biology, Evripidis Gavathiotis, Ph.D., describes previously unknown, small molecules that bind to and inhibit BAX, the protein that plays a key role in causing apoptosis. Dr. Gavathiotis and colleagues also identified a pocket within the BAX protein to which these novel inhibitors bind, thereby stabilizing BAX and preventing it from triggering apoptosis. In in vitro experiments, Dr. Gavathiotis and colleagues showed that the inhibitors protected mouse fibroblasts from apoptotic stimulation. Such BAX inhibitors could potentially be used as drugs to prevent cell death during heart attacks, strokes, neurodegenerative diseases, and chemotherapy or radiation treatment. Dr. Gavathiotis is an associate professor of biochemistry and of medicine at Einstein.