‘Survival protein’ protects the brain against effects of stroke

May 25, 2011

(Credit: stock image)

A “survival protein” that protects the brain against the effects of stroke in rodent brain tissue has been discovered by scientists at Johns Hopkins University. The finding has implications for treating stroke as well as Parkinson’s Disease, diabetes, and heart attack.

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, including the Iduna protein. This protein increased three- to four-fold in preconditioned mouse brain tissue following an insult to the tissue, the scientists said.

The 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, which induced preconditioning. Cells deficient in Iduna did not survive, but those with more Iduna did.

The scientists found that the Iduna protein interferes with a particular kind of cell death that’s implicated in complications from diabetes and heart attack as well as stroke. By binding with a molecule known as PAR polymer, Iduna prevents the movement of cell-death-inducing factor (AIF) into a cell’s nucleus.

“Apparently, what doesn’t kill you makes you stronger,” says Valina Dawson, Ph.D. “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.”

Ref: Shaida A Andrabi, Ho Chul Kang, et al., Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death, Nature Medicine, 2011; DOI: 10.1038/nm.2387

Ref: Y. Wang, N. S. Kim, et al., Poly(ADP-Ribose) (PAR) Binding to Apoptosis-Inducing Factor Is Critical for PAR Polymerase-1-Dependent Cell Death (Parthanatos), Science Signaling, 2011; 4 (167): ra20 DOI: 10.1126/scisignal.2000902