Overexpression of Human Protein Protects Mice from Injury from and Heart Attack

Ultimate goal of research is to identify drugs which boost the body’s attempt to heal itself

November 6, 2006  Mice genetically engineered to overproduce the protein neuroglobin suffer 30 percent less tissue damage following strokes, and 25 percent less damage following heart attacks, when compared to normal mice, researchers at the Buck Institute for Age Research have reported. Results of the study, to be published the week of November 6 in the on-line edition of the Proceedings of the National Academy of Sciences, highlight continued efforts in the laboratory led by David Greenberg, MD, PhD, to identify the body’s natural protective mechanisms with the ultimate goal of finding drugs that boost healing efforts in humans.

Neuroglobin, closely related to hemoglobin (the oxygen-carrying protein in blood), is expressed predominantly in the brain of vertebrate animals, including humans, but its normal function is unknown. In earlier studies, injecting a virus containing the gene for neuroglobin into the brains of mice protected them from stroke.  In this research, strokes and heart attacks were produced in mice that had a genetically programmed overabundance of neuroglobin in brain, heart and other tissues; the results hold the promise that a drug could be developed to encourage the overproduction of neuroglobin in humans, providing the same protective effects.

“We were pleasantly surprised when we found that the excess neuroglobin not only reduced injury from stroke, but also lessened damage to heart muscle following heart attacks,” said Adil Khan, PhD, who led the research team.  “The next step in our research is to clarify the mechanisms involved in the activity of neuroglobin, to make it easier to identify potential drug targets.” Some scientists believe that neuroglobin may protect cells by delivering more oxygen to them, or by increasing blood flow to damaged tissue.

Khan added that the overabundance of the protein appears to have no damaging side effects on the mice. “The ultimate goal of this basic research is to develop a therapeutic,” he said. “The best case scenario is that someday people might be able to take a drug or supplement that boosts neuroglobin production, similar to the iron supplementation used to increase hemoglobin in patients with anemia.” Khan added, “If research plays out in that direction, we would have an opportunity to develop a commonly available drug that could be used to prevent strokes and heart attacks in those at risk for disease.”

Joining Khan and Greenberg in the work include Buck Institute investigators Kunlin Jin, Yaoming Wang, Yunjan Sun, Xiao Ou Mao, Lix Xie, Erin Miles, Justin Grabowski, Sylvia Chen and Lisa M. Ellerby. The work was funded by a grant from the National Institutes of Health.

The Buck Institute is the only freestanding institute in the United States that is devoted solely to basic research on aging and age-associated disease. The Institute is an independent nonprofit organization dedicated to extending the healthspan, the healthy years of each individual’s life.  The National Institute of Aging designated the Buck a “Nathan Shock Center of Excellence in the Biology of Aging,” one of just five centers in the country.  Buck Institute scientists work in an innovative, interdisciplinary setting to understand the mechanisms of aging and to discover new ways of detecting, preventing and treating conditions such as Alzheimer’s and Parkinson’s disease, cancer, arthritis and stroke.  Collaborative research at the Institute is supported by new developments in genomics, proteomics and bioinformatics technology.

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