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The Healthy Aging Program

Lou Gehrig's Disease (ALS), Peroxynitrite, and Superoxide Dismutase


Principal Investigator: Joseph Beckman, Ph.D.

Since 2002, I have served as Director of OSU’s Environmental Health Sciences Center, which is funded by the National Institutes of Health to support research on the role of the environment in causing disease. The Center provides advanced technology that supports LPI researchers with the long-term goal of understanding how we can reduce our susceptibility to environmental stress as we age.

A major research project in my laboratory is aimed at understanding how oxidative stress, superoxide dismutase, and zinc are involved in Lou Gehrig’s disease, also known as amyotrophic lateral sclerosis (ALS). ALS is a dreadful disease caused by the unexplained death of motor neurons that control the movement of all voluntary muscles. We have only about 500,000 motor neurons at birth that cannot be replaced. Mutations in the antioxidant enzyme superoxide dismutase are the first identified cause of ALS. Our research indicates that the loss of zinc from superoxide dismutase is what causes motor neurons to die. We have shown that supporting cells in the spinal cord called astrocytes are key to understanding why the disease progresses. We are also investigating other dietary supplements, such as lipoic acid, acetyl-L-carnitine, and alpha-tocopherol, as possible means to slow the progression of ALS.

The second major project in the laboratory focuses on the roles of nitric oxide, peroxynitrite, and nitrotyrosine in human disease. The major function of superoxide dismutase is to scavenge superoxide, which is an oxygen radical. Nitric oxide also has a “dark side” and, following reaction with superoxide to produce the powerful oxidant peroxynitrite, can promote oxidative and nitrative damage to blood vessels, skin, heart, lung, kidney, and brain.We are characterizing the role of peroxynitrite in injuring cells and how cells respond to this damage.