Parthanatos gives absolutely no sense of urgency which is why we need to always use the term neuronal cascade of death. Neuroprotection is just as useless a term.
Research partners Dr. Ted Dawson, Ph.D., now director of the Institute for Cell Engineering at the Johns Hopkins University School of Medicine, and Valina Dawson, Ph.D., professor of neurology, and their research group conducted experiments on laboratory-grown cells to determine the culprit in the event chain that ultimately causes cell death.
The new research builds on a growing body of knowledge of a distinct form of programmed brain cell death dubbed "parthanatos" by the team in earlier work to distinguish it from other types of cell death, such as apoptosis, necrosis, or autophagic death.
Previous research indicated that when a protein - mitochondrial apoptosis-inducing factor (AIF) - moves from its residing location in the energy-producing mitochondria of the cell to the nucleus, it causes the genome housed in the nucleus to be carved up, leading to cell death.
MIF protein 'chops up DNA,' triggers parthanatos cell deathWhile the transfer of AIF into the nucleus leads to cell death, AIF is not responsible for the DNA being carved. Yingfei Wang, Ph.D., an assistant professor at the University of Texas Southwestern Medical Center, screened thousands of human proteins to identify those that strongly interacted with AIF and could, therefore, be responsible for cutting up the DNA.
Wang identified 160 possible protein candidates and stopped each of them being produced one by one in lab-grown human cells, in order to determine whether cell death would be prevented if one protein was eliminated.
Of all the 160 proteins, the team identified macrophage migration inhibitory factor (MIF) at the heart of the cell-death process.
"We found that AIF binds to MIF and carries it into the nucleus, where MIF chops up DNA. We think that's the final execution step in parthanatos."Additionally, Dr. Dawson and colleagues have discovered chemical compounds that can block the action of MIF in the lab-grown cells and, as a result, protect them from cell death. Future work will focus on testing these effects in animals and modifying the process to increase safety and efficacy.
Dr. Ted Dawson, Ph.D.