Navigation Links
What doesn't kill the brain makes it stronger
Date:5/23/2011

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 turned up the gene's activity in the cells during exposure to the toxic chemical that induced preconditioning. Cells deficient in Iduna did not survive, but those with more Iduna did.

In another series of experiments in live mice, the team injected a toxic chemical into the brains of a control group of normal mice and also into a group that had been genetically engineered to produce three to four times the normal amount of Iduna as if they had been preconditioned. The engineered mice with more Iduna were much less susceptible to brain cell death: They had more functional tissue and markedly reduced stroke damage in their brains. In addition, the Iduna mice were less impaired in their ability to move around in their cages.

"Identifying protective molecules such as Iduna might someday lead to drugs that trigger the brain survival mechanism when people have a stroke or Parkinson's disease," says Ted Dawson, M.D., Ph.D., Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases and scientific director of the Johns Hopkins Institute for Cell Engineering.

In research published April 5 in Science Signaling, the Dawsons' laboratories previously revealed the mechanism that underpins AIF's pivotal role in parthanatos.

By studying the 3-D structure of AIF, the team first identified the molecular pocket that looked like a potential PAR binding site. They then swapped that region out for a different one to see if it indeed took up PAR. Using HeLa cells in addition to mouse nerve and skin cells, the scientists noted that the AIF with the swapped region did not bind PAR and was not able to move into the nucleus.

The team genetically manipulated neurons so that they didn't make any AIF, then in some cells added wild-type AIF, and in others added an AIF that did not bind PAR. When those cells were stressed using the "stroke in a dish" technique, the cells with normal AIF died while those with the AIF that could not bind PAR did not, revealing that PAR binding to AIF is required for parthanatos.

"These findings suggest that identifying chemicals that block PAR binding to AIF could be very protective," says Ted Dawson. "On the other hand, identifying chemicals that mimic the effect of PAR polymer could be novel therapeutic agents that would kill cancers by causing cell death."


'/>"/>

Contact: Maryalice Yakutchik
myakutc1@jhmi.edu
443-287-2251
Johns Hopkins Medical Institutions
Source:Eurekalert

Related biology news :

1. Penn biophysicists create new model for protein-cholesterol interactions in brain and muscle tissue
2. During exercise, the human brain shifts into high gear on alternative energy
3. Millisecond brain signals predict response to fast-acting antidepressant
4. Food for thought -- regulating energy supply to the brain during fasting
5. Risk and reward compete in brain
6. Brainy genes, not brawn, key to success on mussel beach
7. Brain-nourishing molecule may predict schizophrenia relapse
8. Brain structure provides key to unraveling function of bizarre dinosaur crests
9. MU brain imaging center provides research for autism, schizophrenia and Parkinsons disease
10. Key to function of dinosaur crests found in brain structure
11. Emotion and scent create lasting memories -- even in a sleeping brain
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/2/2016)... Feb. 2, 2016 Technology Enhancements Accelerate Growth of ... of the digital and computed radiography markets in ... and Indonesia (TIM). It provides ... size, as well as regional market drivers and restraints. ... market penetration and market attractiveness, both for digital and ...
(Date:2/1/2016)... , Feb. 1, 2016  Today, the first ... (AHA) announced plans to develop a first of its ... power of IBM Watson. In the first application of ... IBM (NYSE: IBM ), and Welltok will create ... health assessments with cognitive analytics, delivered on Welltok,s health ...
(Date:1/25/2016)...   Unisys Corporation (NYSE: UIS ) today announced ... International Airport, New York City , to help ... to enter the United States using passports ... pilot testing of the system at Dulles last year. The ... during January 2016. --> pilot testing of the ...
Breaking Biology News(10 mins):
(Date:2/3/2016)... WARRINGTON, Pa. , Feb. 3, 2016 /PRNewswire/ ... biotechnology company focused on developing aerosolized KL4 surfactant ... Board of Directors has approved an inducement award ... Craig Fraser , its newly appointed President and ... the Board,s Compensation Committee on February 1, 2016 ...
(Date:2/3/2016)... COPENHAGEN, Denmark , Feb. 3, 2016 ... stage biotechnology company that applies its innovative TransCon technology ... to present at an upcoming investor conference.Event:2016 Leerink Partners ... York, NY Date:  , Wednesday, February 10, 2016 Time:  ... --> www.ascendispharma.com . --> An audio ...
(Date:2/3/2016)... BRUNSWICK, N.J. , Feb. 3, 2016 /PRNewswire-USNewswire/ ... grants totaling more than $1 million for researchers ... are working on health-related research that demonstrates exciting ... this round of funding for the New Jersey ... for faculty members at these educational institutions— Princeton ...
(Date:2/3/2016)... ... February 03, 2016 , ... ProMIS ... potential targets (epitopes) specific to misfolded, propagating strains of Amyloid beta involved in ... antibody therapeutics for Alzheimer’s. , Following on from the first misfolded Amyloid beta ...
Breaking Biology Technology: