New Way to Trigger Brain to Release Antioxidants

Until this finding, researchers were not able to trigger the release of these certain antioxidants directly in nerve cells, at the site where damage and degeneration occurs.
In stroke and various neurodegenerative disorders, such as Alzheimer's disease and Lou Gehrig's disease, glutamate, an amino acid found in high quantities in the brain, is thought to build up. At normal concentrations, glutamate acts as a neurotransmitter that nerves use to communicate. However, at excessive levels glutamate is toxic, resulting in overstimulation of nerve cells, known as excitotoxicity, and causing excessive stress on the nerve cells, ultimately ending in cell death.

The new research suggests that neurite outgrowth-promoting prostaglandins (NEPPs), compounds that accumulate in nerve cells, prevent nerve damage by triggering the Keap1/Nrf2 pathway that regulates the production of antioxidants, which relieve cells of damaging free radicals that result from excitotoxicity.

"This is the first reported evidence that this protective response can be activated directly in nerve cells to release antioxidants and counter oxidative stress,” remarked Stuart Lipton, M.D., Ph.D., director of the Del E. Webb Center for Neurosciences and Aging at the Burnham Institute (La Jolla, CA, USA) and senior author of the study, published in the January 17, 2006, issue of the journal Proceedings of the [U.S.] National Academy of Sciences. "These findings provide support for further investigation of NEPP drugs to potentially treat ischemic stroke, multiple sclerosis, Alzheimer's disease, Lou Gehrig's disease, and other neurodegenerative disorders.”

The investigators discovered that NEPPs were able to stimulate the knKeap1/Nrf2 pathway in nerve cells that is designed to protect against oxidative and nitrosative stress (which produces free radicals) and excitotoxicity. The pathway regulates the production of natural antioxidants, such as bilirubin, that can protect against oxidative stress caused by ischemic stroke and degenerative disorders.

The Japanese investigators involved in the study were from Iwate University, Osaka City University, Gifu University, and Iwate Medical University.




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Burnham Institute