Drugs target Nox2 enzyme directly instead of acting as antioxidants
Scientists at Emory University School of Medicine have identified a new type of anti-inflammatory compound that may be useful in treating a wide range of conditions, including neurodegenerative and autoimmune diseases. These compounds inhibit the enzyme Nox2, part of a family of enzymes responsible for producing reactive oxygen species (ROS).
The results were published Thursday in the journal Chemistry & Biology.
"Nox2 inhibitors could be valuable with many conditions where inflammation plays a role," says senior author David Lambeth, MD, PhD, professor of pathology and laboratory medicine at Emory University School of Medicine.
ROS and the Nox enzymes play vital roles in the immune and cardiovascular systems, but too much ROS leads to oxidative stress, linked with tissue damage and conditions such as stroke, heart failure and neurodegenerative diseases.
Antioxidants are supposed to absorb ROS, but many clinical studies examining antioxidants' benefits have been disappointing. Compounds that inhibit the Nox enzymes would stop ROS production at the source, rather than mop them up like antioxidants do.
"We are taking a completely different approach," says first author Susan Smith, PhD, Emory research assistant professor of pathology and laboratory medicine. "If a burst pipe is gushing water all over the basement, the first thing you need is a wrench to stop the water from flowing, instead of a mop."
The Nox inhibitors that were already available to researchers are not specific enough for one enzyme over another. Smith collaborated with research scientist Jaeki Min and colleagues at the Emory Chemical Biology Discovery Center and Emory Institute for Drug Development to screen for compounds that inhibit Nox2. In particular, they searched for compounds that interfere with assembly of the Nox2 enzyme rather than targeting the catalytic site.