Jeffery Cox, microbiologist and tuberculosis expert at UC San Francisco, and his team discovered that a protein called Parkin, which is associated with a loss of nerve cells in Parkinson’s disease and also plays a key role in causing the destruction of tuberculosis bacteria. Tuberculosis is an infectious disease that kills 1.4 million people each year globally, and the tuberculosis bacteria spreads from person to person through the air. Parkinson’s disease is the most common neurodegenerative movement disorder that affects millions of people worldwide, mostly elderly people.
Activating the enzyme Parkin could prove to be effective in not only treating Parkinson’s disease but also in protecting against tuberculosis, according to Cox. The study appeared in the journal Nature on September 4th, 2013.
When cells are invaded by mycobacterium, macrophage in those cells attempts to gobble up the foreign bacteria to degrade them (a process called xenophagy). Mycobacterium, such as tuberculosis and salmonella, secrete a protein that degrades the sac of macrophage. The most abundant and crucial components that cells need to dispose of are mitochondria, metabolic powerhouses providing energy for everyday housekeeping chores of cells. Mitochondria often require replacement, and this process, called mitophagy, depends on Parkin.
Cox became curious about the enzyme when he learned its genetic variations are associated with increased susceptibility to tuberculosis infection. In a study, Parkin-lacking mice died when they were infected with M. tuberculosis, while normal mice survived infection. “Because of the commonalities between mitophagy and the xenophagy of intracellular mycobacteria, as well as the links between Parkin gene polymorphisms and increased susceptibility to bacterial infection in humans, we speculated that Parkin may also be recruited to M. tuberculosis and target it for xenophagy,” Cox said.
Cox and his colleagues, one of which is Michael Shiloh, MD, PhD, from the University of Texas Southwestern Medical Center in Dallas, are working to boost Parkin activity against cell-invading bacteria. “We are exploring the possibility that small-molecule drugs could be developed to activate Parkin to better fight tuberculosis infection,” he said.