Overexpression of Human Protein Reduces Severity of Alzheimer's Disease in Mice

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

November 8, 2006  Mice genetically engineered to both overproduce the protein neuroglobin and to develop Alzheimer’s disease (AD) had a much milder form of the disease when compared to mice engineered to have AD alone, researchers at the Buck Institute for Age Research have reported. Results of the study, to be published the week of November 12 in the on-line edition of the Proceedings of the National Academy of Sciences, highlight continued efforts by Buck faculty member David Greenberg, MD, PhD and lead author Adil Khan, PhD, and colleagues 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 this study, the AD mice who overexpressed neuroglobin performed significantly better on a memory test and had less of the sticky deposits commonly associated with the neurodegenerative disease.

In earlier studies, an overexpression of neuroglobin was found to protect mice from nerve damage following stroke and to lessen damage from heart muscle following heart attacks. 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 are now screening existing drugs and chemical compounds to find those that prompt the body to produce more neuroglobin,” said Greenberg.

Joining Greenberg and Khan in the work include Buck Institute investigators Kunlin Jin,  Xiao Ou Mao, and Surita Banwait. 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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