By Susan E. Matthews
Chronic inflammatory conditions, such as Crohn’s disease, psoriasis, rheumatoid arthritis or multiple sclerosis, can be debilitatingly painful to live with and treat. New revelations about the specific protein that triggers the process that leads to inflammation, however, provides a hopeful new target for treatments that could reduce inflammation and help treat these conditions, according to a study published in Immunity.
Researchers from Melbourne, Australia have pinpointed the role protein MLKL plays in triggering cell death. As a result of the three-dimensional images they were able to create of the protein, the researchers believe it could be a new target for therapies.
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Normally, when a virus or bacteria attacks the human body, the affected cells are able to self-destruct, in hopes of limiting the body’s exposure and illness. In fact, in response to particularly strong bacteria or viruses, the cell not only self-destructs, it sends a message to other cells to alert them of the disease’s presence. This activates the immune system’s defense against a virus, a process called necroptosis.
But for people with inflammatory conditions, this alert system is activated when there is no threat, and thus the immune system overreacts, causing inflammation and even diseases that stem from inflammation.
MLKL is critical to activating the cells’ alert response, so the researchers used the Austrailian Sychrotron to create 3D images of the enzyme. They discovered a difference between MLKL and other enzymes, namely that it is a “dead enzyme,” the researchers said, meaning that “MLKL needs to be ‘switched on,’” prior to activating the response, said study author James Murphy, MD, of the Walter and Eliza Hall Institute in Australia.
“MLKL could therefore be a perfect target for treatments because it is different from almost every other cell-signaling protein, making it easier to develop highly specific drugs and limiting potential side effects,” Murphy said in a statement.
The next step for the researchers is to determine the different enzyme states when it’s switched on and switched off, the researchers said, to understand how to use drugs to block the ‘on’ state.
“"We are already using this knowledge to develop specific, drug-like molecules to test in disease models,” said study author John Silke, and associate professor at the Institute. “This could directly lead to treatments that will help patients who have chronic inflammatory diseases.”
While the paper’s basic science seems sound, Atsushi Sakuraba, MD, instructor of medicine at the University of Chicago Medical School warned that it is “very premature to refer to this as a potential target of treatment.” Dr. Sakuraba, who treats Crohn’s disease and colitis, said that the role of necroptosis in causing inflammatory diseases is still unclear, so it remains to be seen whether blocking MLKL will be helpful.
“First we have to define what the role of necroptosis is in immune-mediated inflammatory conditions, and after, whether blocking it would benefit the disease,” he said.
Currently, the cause of several inflammatory conditions is still unknown, and treatment essentially consists of managing symptoms, Sakuraba noted.
"Researchers Target New Enzyme for Treatment of Inflammatory Conditions" originally appeared on Everyday Health.