Johns Hopkins scientists say that a newly discovered "survival protein" protects the brain against the effects of stroke in rodent brain tissue by interfering with a particular kind of cell death that's also implicated in complications from diabetes and heart attack.
Reporting in the May 22 advance online edition of Nature Medicine, the Johns Hopkins team says it exploited the fact that when brain tissue is subjected to a stressful but not lethal insult a defense response occurs that protects cells from subsequent insult. The scientists dissected this preconditioning pathway to identify the most critical molecular players, of which a newly identified protein protector called Iduna -- is one.
Named for a mythological Norwegian goddess who guards a tree full of golden apples used to restore health to sick and injured gods, the Iduna protein increased three- to four-fold in preconditioned mouse brain tissue, according to the scientists.
"Apparently, what doesn't kill you makes you stronger," says Valina Dawson, Ph.D., professor of neurology and neuroscience in the Johns Hopkins Institute of Cell Engineering. "This protective response was broad in its defense of neurons and glia and blood vessels the entire brain. It's not just a delay of death, but real protection that lasts for about 72 hours."
The team noted that Iduna works by interrupting a cascade of molecular events that result in a common and widespread type of brain cell death called parthanatos often found in cases of stroke, Parkinson's Disease, diabetes and heart attack. By binding with a molecule known as PAR polymer, Iduna prevents the movement of cell-death-inducing factor (AIF) into a cell's nucleus.
In some of the experiments, Dawson and her team exposed mouse brain cells to short bursts of a toxic chemical, and then screened these "preconditioned" cells for genes that turned on as a result of the insult. Focusing on Iduna, the researchers
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Johns Hopkins Medical Institutions