University Of Kentucky Chandler Medical Center Researchers Identify Protein That,,May Cause Nerve Cell Death In Alzheimer's Disease

He demonstrated several years ago that Par-4 was conspicuously present in prostate cancer cells undergoing apoptosis as a result of androgen(testosterone) removal. Testosterone removal is a common treatment for prostate cancer that can reduce the formation of tumors of the prostate gland in humans.

Rangnekar said that Mattson became aware of his cancer research and suggested that Par-4 might play a role in the same molecular processes that occur in neurodegenerative disorders.

To investigate the protein's effects, Mattson and Qing Guo, Ph.D., genetically engineered nerve cell cultures that blocked the ability of the Par-4 protein to function. The cells became remarkably resistant to death.

"This suggests the necessity of the Par-4 gene in the molecular cascade of events that signals the beginning of cell death," Mattson said. "Our cell culture data demonstrate that Par-4 is expressed during the early stages of the cell death process."

Factors such as environmental stimulants and genetic predisposition might trigger the cell death chain of events. Once set into motion, other genes and proteins help trigger the "switches" to signal cell death. Mattson and Rangnekar continued to pursue other factors that might interact with Par-4.

In earlier studies, Mattson's team gathered evidence that a protein called amyloid-beta protein, which abnormally accumulates in the brains of Alzheimer's patients by forming structures called plaques, can cause apoptosis in cultured rat and human neurons. Amyloid-beta protein increases free radical levels in cells and disrupts the ability of nerve cells to maintain proper calcium levels -- both are contributors to cell demise.

Cell culture experiments in the present study demonstrated that Par-4 made nerve cells more vulnerable to being killed by amyloid-beta protein, and that levels of free radicals and calcium were increased within the cells. When Par-4 was blocked,

Contact: Kim Cumbie
(606) 323-6363
University of Kentucky Medical Center

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