Oxidation of potassium channel in cells linked to loss of neuronal function in aging

Researchers at UMDNJ-Robert Wood Johnson Medical School are one step closer to determining how human cells can be protected against the affects of age-related neurodegeneration including Alzheimer's and Parkinson's disease.

The findings, published this past month in Nature Neuroscience, link the oxidation of potassium channels, which control a variety of cell functions and are essential to neuronal function, to the loss of neuronal function in aging. The study further shows that the oxidation process can be blocked by modifying the potassium channel, thereby making it resistant to age-related deterioration.

The study was conducted by Federico Sesti, PhD, associate professor, Shi-Qing Cai, PhD, research associate, both in the department of physiology and biophysics. The research was supported by a grant from the National Institutes of Health.

Oxygen metabolism (the process by which living cells produce energy), leads to the production of highly reactive oxygen species (ROS), which can cause significant neurodegenerative damage in cells that are unable to protect themselves. This is seen most remarkably in aging cells, which experience both an increase in ROS production and a decrease in defense mechanisms, a condition known as oxidative stress.

Through their examination of cells in the laboratory, the researchers concluded that potassium channels are targets of ROS, resulting in modification to the cell that causes neuronal dysfunction. The researchers showed that by modifying a single cysteine residue, they could make the potassium channel resistant to oxidation, thereby allowing for normal functioning of the nervous system.

"ROS is a natural product of cell metabolism and normal, young cells are known to be resistant to its negative affects, however uncontrolled ROS can cause considerable damage to proteins, DNA and cell membranes," said Dr. Sesti. "It was our goal to determine the mechanism underlying age-related cell dysfunction and if there was a method to safeguard aging cells from damage. This discovery provides a foundation for developing therapies for neurodegenerative disorders, including multiple sclerosis and cardiovascular disease."

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