Strokes, injuries and even neurological diseases such as Alzheimer's, Parkinson's or Huntington's seem to follow the same chain of events, in spite of their distinct triggers. New research has found the end of the chain, responsible for the fatal step through carving up a cell's DNA. The conclusions of the research create new possibilities in the development of drugs aimed at treating and even preventing the process.
The study, published on Oct. 7 in Science, documents the experiments conducted inside lab-grown cells, signed by Ted Dawson, director of the Institute for Cell Engineering at the Johns Hopkins University School of Medicine, and Valina Dawson, professor of neurology.
Cell death occurs because of the toxic and/or stressful insults, and a scientific way to stop its activity would represent a huge step in the fight against neurodegenerative disorders, as well as any other form of cell injury.
The shared mechanisms of these diseases share a programmed brain cell death the team named parthanatos, which is an enzyme involved in almost all forms of cellular injuries.
Other scientific studies showed that a protein named mitochondrial apoptosis-inducing factor (AIF) sometimes leaves its normal place in the cellular mitochondria moving toward the nucleus, triggering the carving up of the genome housed in the nucleus. The process is responsible for cell death.
However, AIF cannot cut DNA alone. The endonuclease G promotes DNA degradation cooperating with AIF but doesn't play an important role in the chromatinolysis that is PARP-dependend, therefore not being responsible for cell death.
But Yingfei Wang, assistant professor at the University of Texas Southwestern Medical Center, tested which proteins interact most powerfully with the AIF by screening other human proteins. Using custom molecules known as small interfering RNAs, she tried to stop the formation of proteins in human cells grown in her laboratory to test the hypothesis of preventing cell death.
Of the total number of proteins, the macrophage migration inhibitory factor (MIF) was the one found responsible for the interaction. Although MIF's capacity to affect DNA was only clearly linked to stroke. Disabling the MIF gene in mice reduced the number of strokes.
The paper also mentioned that some chemical compounds blocking the action of MIF in the cells grown in the lab protected them from parthanatos. According to the scientists, they also plan on testing them on animals to maximize the efficiency.
"We're interested in finding out whether MIF is also involved in Parkinson's, Alzheimer's and other neurodegenerative diseases," explained Dawson.
Blocking the interaction of the two or the entire nuclease activity of MIF would open a major line of therapeutic opportunities for patients of various diseases.