MIF as a Path to Reduce Cell Death Following Stroke
A number of genes and proteins are turning out to be important in the processes of cell death that occur following a stroke or similar injury involving ischemia followed by reperfusion of tissue. It is the return of blood supply that leads directly to cell death, not the initial loss of blood supply. To pick one example from past research, absence of PHD1 has been shown to greatly reduce damage following stroke. Here, researchers investigate a similar functional role for macrophage migration inhibitory factor, MIF, representative of a range of other work along the same lines. These various genes and mechanisms are all windows onto the same core processes of programmed cell death in response to circumstances:
One particular protein is the final executioner of events that result in the death of brain cells during stroke, researchers report. This finding could ultimately lead to new ways to protect against brain damage. Researchers discovered that the protein, macrophage migration inhibitory factor (MIF), breaks the cell's DNA, resulting in brain cell death. The study outlines three possible ways to manipulate MIF to protect brain tissue during a stroke - and possibly in other brain-damaging conditions such as Alzheimer's, Parkinson's, and Huntington's diseases, although this study examined only stroke. Researchers screened thousands of human proteins to find 160 that could be the culprits behind stroke-induced cell death. Eventually, the researchers were able to narrow the field to just one - MIF, a protein long known for its roles in immunity and inflammation.
The MIF finding is the final piece in a puzzle that researchers have been carefully assembling for years to reveal the process by which brain cells die. Despite their very different causes and symptoms, brain injury, stroke, and Alzheimer's, Parkinson's, and Huntington's diseases have a shared mechanism involving a distinct form of "programmed" brain cell death called parthanatos, researchers said. The name comes from the personification of death in Greek mythology, and PARP, an enzyme involved in the cell death process. "I can't overemphasize what an important form of cell death it is; it plays a role in almost all forms of cellular injury." The researchers are working to identify chemical compounds that could block MIF's actions and possibly protect brain cells from damage.
Link: http://www.utsouthwestern.edu/newsroom/news-releases/year-2016/oct/mif-wang.html