New route to cell death found

Damaged or unusable cells in our bodies will commit suicide to protect us from harm. That’s a well-known process with the awkward name of “apoptosis.” There’s also necrosis, meaning “to make dead,” when brain, heart, and other cells die from disease and trauma. These suicides and uncontrolled deaths have always been thought of as separate processes, comparable to killing one’s self as opposed to dying by accident or malignancy.

Now a connection has been found between them. Researchers at Harvard Medical School have uncovered a common pathway by which necrosis can take over when apoptosis runs out of energy. The same scientists have also discovered how to brake the necrosis part, a finding that might lead to new treatments for everything from Alzheimer’s disease to heart attacks and strokes.

Taking their experiments one step further, the researchers have looked for and found a molecule that can block necrosis-like cell death in mice undergoing strokes. If it works as well in humans, it could provide physicians with extra time to limit the deadly and disabling effects of strokes.

“We have found a new pathway to cell death,” says Junying Yuan, a professor of cell biology in whose lab the research was done. “We used to think that, in necrosis, cells get so sick they break apart and die in a completely unregulated fashion. That would make it impossible to develop specific drugs to block such deaths. Now we know there’s more to it than that. We have started to understand that a general process exists to allow cells to die by necrosis when apoptosis fails. That process provides a target for drug therapy. This is very important for medicine because necrosis is so common in human diseases. Furthermore, we have already found a compound that blocks a critical step on the road to necrosis.”

Yuan and her colleagues describe this research and its human potential in the cover story in the July issue of Nature Chemical Biology. The colleagues include Alexei Degterev of Harvard Medical School and others from Massachusetts General and Brigham and Women’s hospitals in Boston and The Tokyo Metropolitan Institute of Medical Science in Japan.