Chemical reaction keeps stroke-damaged brain from repairing itself

Stuart A. Lipton, M.D., Ph.D., is director of the Del E. Webb Neuroscience, Aging, and Stem Cell Research Center at Sanford-Burnham Medical Research Institute and a clinical neurologist. Credit: Sanford-Burnham Medical Research Institute

Nitric oxide, a gaseous molecule produced in the brain, can damage neurons. When the brain produces too much nitric oxide, it contributes to the severity and progression of stroke and neurodegenerative diseases such as Alzheimer's. Researchers at Sanford-Burnham Medical Research Institute recently discovered that nitric oxide not only damages neurons, it also shuts down the brain's repair mechanisms. Their study was published by the Proceedings of the National Academy of Sciences the week of February 4.

"In this study, we've uncovered new clues as to how natural chemical reactions in the brain can contribute to brain damage—loss of memory and cognitive function—in a number of diseases," said Stuart A. Lipton, M.D., Ph.D., director of Sanford-Burnham's Del E. Webb Neuroscience, Aging, and Center and a clinical neurologist.

Lipton led the study, along with Sanford-Burnham's Tomohiro Nakamura, Ph.D., who added that these new molecular clues are important because "we might be able to develop a new strategy for treating stroke and other disorders if we can find a way to reverse nitric oxide's effect on a particular enzyme in ."

Nitric oxide inhibits the neuroprotective ERK1/2 signaling pathway

Learning and memory are in part controlled by NMDA-type glutamate receptors in the brain. These receptors are linked to pores in the nerve cell membrane that regulate the flow of calcium and sodium in and out of the nerve cells. When these get over-activated, they trigger the production of nitric oxide. In turn, nitric oxide attaches to other proteins via a reaction called S-nitrosylation, which was first discovered by Lipton and colleagues. When those S-nitrosylated proteins are involved in cell survival and lifespan, nitric oxide can cause to die prematurely—a hallmark of neurodegenerative disease.

In their latest study, Lipton, Nakamura and colleagues used cultured neurons as well as a living mouse model of stroke to explore nitric oxide's relationship with proteins that help repair neuronal damage. They found that nitric oxide reacts with the enzyme SHP-2 to inhibit a protective cascade of molecular events known as the ERK1/2 signaling pathway. Thus, nitric oxide not only damages neurons, it also blocks the brain's ability to self-repair.

Related Stories

Alzheimer's disease linked to mitochondrial damage

Apr 02, 2009

Investigators at Burnham Institute for Medical Research (Burnham) have demonstrated that attacks on the mitochondrial protein Drp1 by the free radical nitric oxide—which causes a chemical reaction called S-nitrosylation—mediates ...

New pathway to Parkinson's and Alzheimer's diseases

Jul 29, 2010

Although their genetic underpinnings differ, Alzheimer's disease, Parkinson's disease and Huntington's disease are all characterized by the untimely death of brain cells. What triggers cell death in the brain? According to ...

Nitric oxide shown to cause colon cancer

Jan 20, 2009

(PhysOrg.com) -- Researchers long ago established a link between inflammation, cancer and the compound nitric oxide, which may be produced when the immune system responds to bacterial infections, including those of the colon. ...

Multiple axons and actions with PSD-95

Dec 15, 2008

Nitric oxide gets neurons together. And it seems to do it backward. Work by Nikonenko et al. suggests that a protein called PSD-95 prompts nitric oxide release from postsynaptic dendritic spines, prompting ...

Recommended for you

A new way to diagnose malaria, using magnetic fields

15 hours ago

Over the past several decades, malaria diagnosis has changed very little. After taking a blood sample from a patient, a technician smears the blood across a glass slide, stains it with a special dye, and ...

How Alzheimer's peptides shut down cellular powerhouses

Aug 29, 2014

The failing in the work of nerve cells: An international team of researchers led by Prof. Dr. Chris Meisinger from the Institute of Biochemistry and Molecular Biology of the University of Freiburg has discovered ...

User comments