Mechanisms Behind Brain Cell Death Discovered

Findings could translate into preventative treatments for Alzheimer’s and Parkinson’s diseases.

Investigators from John Hopkins University have discovered the critical protein involved in brain cell death resulting from strokes, injuries, and neurodegenerative diseases.

Although reasons behind the cell death differ between the conditions, their findings suggest that this protein is the end of the events and cuts up a cell’s DNA. This could potentially lead to treatments that prevent this process.

A study published by Science based on earlier findings was conducted using laboratory-grown cells. During the previous studies, investigators discovered that different causes of brain cell death shared the same type of programmed cell death called parthanatos.

“I can’t overemphasize what an important form of cell death it is; it plays a role in almost all forms of cellular injury,” said researcher Ted Dawson, MD, PhD.

The investigators have spent numerous years outlining the mechanisms of parthanatos and the proteins involved. They have recently finished detailing the chain of events involved.

It was previously discovered that when mitochrondrial apoptosis-inducing factor leaves the mitochondria and moves to the nucleus, it sparks the carving up of the DNA, which leads to cell death, according to the study.

However, mitochondrial apoptosis-inducing factor (AIF) cannot cut DNA itself, so investigators explored thousands of proteins to determine which had the strongest interaction with AIF. They discovered 160 proteins that elicited the desired response.

The investigators then used small interfering RNAs to stop the protein’s production in lab-grown cells, and found that macrophage migration inhibitory factor (MIF) was the protein involved in cell death.

“We found that AIF binds to MIF and carries it into the nucleus, where MIF chops up DNA,” Dr Ted Dawson said. “We think that’s the final execution step in parthanatos.”

Additionally, the investigators identified chemical compounds that blocked the macrophage migration inhibitory factor’s action, which prevents parthanatos, according to the study.

Future studies will be conducted to test their findings in animal models, and will then modify the compounds for increased safety and efficacy.

However, investigators said that their macrophage migration inhibitory factor’s ability to cut DNA has only been linked to stroke thus far. If their findings translate to other diseases, numerous treatment options could be created for diseases such as Alzheimer’s disease and even the rarer condition, Huntington’s disease.

“We’re interested in finding out whether MIF is also involved in Parkinson’s, Alzheimer’s and other neurodegenerative diseases,” Dr Dawson concluded.