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DECEMBER 2006

Study Identifies Enzyme Responsible for Brain Deterioration in Alzheimer’s
Univ. of Missouri-Columbia Researchers Hope Findings Lead To A Medical Breakthrough

Researchers at the University of Missouri-Columbia identified an enzyme responsible for the deterioration of brain function for people with Alzheimer’s disease, reported in the Journal of Neuroscience.

James Lee, assistant professor of biological engineering in the College of Engineering, and his former doctoral student Donghui Zhu, currently a post-doctoral research associate at Columbia University, conducted their research in collaboration with Grace Sun, professor of biochemistry and pathology and anatomical sciences in the Missouri U (MU) School of Medicine and College of Agriculture, Food and Natural Resources. Sun also directs an Alzheimer’s project at MU that is being funded by the National Institutes of Health.

The research team’s work focused on amyloid-beta peptide, a common neuron-killing toxin found in the brains of Alzheimer’s patients, and astrocytes, which supports neurons and is the major cell in the brain. In lab tests, they studied how the toxin affects and interacts with the cell to activate a critical enzyme—phospholipase A2. Lab tests showed that with increased activity, phospholipase A2 negatively affected the mitochondria, which is responsible for energy production, resulting in increased oxidative stress. Zhu and Lee said an increase in oxidative stress further promotes neuron death, worsens the disease and causes decreased energy levels.

It’s an important aspect in the development of Alzheimer’s disease,” Zhu said. An increase in oxidative stress, Lee said, is one of the characteristics found in the brains of Alzheimer’s patients. Zhu and Lee hope their findings lead to a medical breakthrough and the design of effective drugs to treat people living with the brain disorder that gradually destroys a person’s memory and ability to communicate and carry out daily activities.

 “Alzheimer’s is a complicated disease,” Lee said. “We know that phospholipase A2 is one of the key factors. If we can regulate phospholipase A2, maybe it can become part of the therapeutic strategy for treating Alzheimer’s.”#

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