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UK, U of L Researchers Collaborate
to Find New Answers on Alzheimer's Disease

By Jennifer Bonck

Jon Klein, left, of the University of Louisville School of Medicine listens as UK chemistry professor Allan Butterfield discusses their collaboration. UK graduate student Alessandra Castegna is at right.

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"This new method of identifying minute amounts of oxidized proteins has the potential of providing insight into the mechanisms of neuronal death in AD."

-- Allan Butterfield, professor of chemistry

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Sept. 5, 2002 (Lexington, Ky.) -- A joint project of University of Kentucky and University of Louisville researchers has used innovative scientific technology to identify oxidized proteins involved in Alzheimer's disease (AD). The findings may lead to a greater understanding of this devastating disease.

Allan Butterfield, Ph.D., professor of chemistry, and Alessandra Castegna, graduate student in the department of chemistry, UK College of Arts and Sciences, have been working on the project, funded by the National Institute on Aging, a division of the National Institutes of Health (NIH). Jon Klein, M.D., Ph.D., professor of medicine and biochemistry and molecular biology, and director, Core Proteomics Laboratory, University of Louisville School of Medicine, has been of integral assistance to Butterfield's UK team.

Butterfield has used proteomics to identify specifically oxidized proteins involved in AD. Proteomics is used to study how proteins affect the behavior of cells, tissues, and organs. By studying how proteins behave in certain instances, researchers hope to gain a greater understanding of disease processes. This isthe first time that the method has been used to identify oxidized proteins involved in AD.

Proteomics technology separates proteins, in this case from AD and control brains, in two dimensions and analyzes them by mass spectrometry, a sophisticated imaging technique, following digestion with enzymes.

"Scientific developments over the last ten years have greatly advanced the capabilities and potential of this method," said Klein.

The research team has found three proteins to be specifically oxidatively modified in AD brains-creatine kinase, glutamine synthetase, and ubiquitin C-terminal hydrolase. The results of the study have been published in Free Radical Biology & Medicine.

AD is the most common form of dementia among the elderly in the world, and there are an estimated four to five million cases in the United States alone.

"This new method of identifying minute amounts of oxidized proteins has the potential of providing insight into the mechanisms of neuronal death in AD," said Butterfield.


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