25 May 2011

We have a stroke, and we are getting stronger!

Researchers at Johns Hopkins University, working under the guidance of Professor Valina Dawson, claim that the Iduna protein they identified protects neurons, as well as glial cells and blood vessels of the rodent brain from the destructive effects of stroke, blocking the mechanism of a certain type of cell death, also observed in complications of diabetes and myocardial infarction.

A serious but non-fatal stroke triggers mechanisms in the brain tissues that provide effective protection of cells from subsequent strokes within 72 hours. The result of studying these mechanisms was the identification of the Iduna protein, named after the Norse goddess who protects a tree with golden apples that heal the gods from diseases and injuries.

Scientists have found that Iduna acts by blocking a cascade of molecular signals leading to parthanatos, a type of brain cell death often seen in strokes, Parkinson's disease, diabetes and myocardial infarction. By binding to a molecule known as PAR-polymer –poly(ADP-ribose) polymerase-1, Iduna prevents the penetration of the cell death induction factor (AIF, apoptosis-inducing factor) into the cell nucleus.

During one of the series of experiments, scientists briefly exposed mouse brain cells to toxic compounds, after which they screened such "prepared" cells to identify genes that were activated in response to exposure. It turned out that the chances of cells to survive and obtain the status of "prepared" were directly proportional to the activity of the gene encoding the Iduna protein.

The figure shows a section of the brain after exposure to a toxic compound that would normally kill cells. In "prepared" neurons, the AIF (blue) protein is stored in the mitochondria – the energy centers of the cell.

In another series of experiments, a toxic compound was injected into the brains of control mice and into the brains of genetically modified animals whose brain cells synthesized 3-4 times more Iduna than cells of normal animals. As expected, the mice of the experimental group were less susceptible to the effects of toxins. They retained more functioning brain tissue and had significantly fewer consequences of a heart attack (blood supply disorders) of the brain. Their motor functions were also preserved much better compared to the animals of the control group.

Experts believe that the identification of protective molecules like Iduna in the future will allow the development of drugs that trigger protective mechanisms in the brain tissue of patients with Parkinson's disease, as well as stroke survivors.

Article by Andrabi et al. Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death is published on May 22 in the preliminary on-line version of the journal Nature Medicine.

Evgeniya Ryabtseva
Portal "Eternal youth" www.vechnayamolodost.ru Based on Johns Hopkins Medicine: What Doesn't Kill The Brain Makes It Stronger. 

25.05.2011


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