Brain cell dysfunction in low oxygen is, surprisingly, caused by the very same responder system that is intended to be protective, according to a new published study by a team of researchers at Case Western Reserve University School of Medicine.

“These powerful protein responders initially protect brain cells from low oxygen as expected, but we find that their prolonged activity leads to unintended collateral damage that ultimately impairs brain cell function,” said the study’s principal investigator Paul Tesar, a professor in the Department of Genetics and Genome Sciences at the School of Medicine and the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics.

Defining the mechanism of brain-cell damage in low oxygen conditions provides an opportunity to develop effective therapies, including a class of drugs studied in their research that could inform future clinical approaches for many neurological diseases caused by low oxygen. The work also clarifies how the response to low oxygen causes disease in other tissues outside the brain.

Their research was published online Oct. 21 in the journal Cell Stem Cell.