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MLKL Study Offers Hope For New Anti-Inflammatory Treatments

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Australian researchers from the Walter and Eliza Hall Institute have made important discoveries related to a protein called MLKL, more specifically its role in the necroptosis pathway. Having revealed the structure of this protein, the scientists are hoping to develop new treatments for chronic inflammatory diseases such as rheumatoid arthritis, Crohn´s disease and psoriasis.

Necroptosis is the back-up plan that infected cells activate when viruses or bacteria prevent them from self-destructing via the standard process, which is known as apoptosis. As associate professor John Silke explains, necroptosis is still cell suicide but it allows the irreparably damaged cell to alert the immune system so that it can respond to the intrusion. At times, however, the necroptosis pathway could be triggered inappropriately, prompting the immune system to act in a way that stimulates the development of inflammatory diseases.

Another team member, Dr James Murphy, said that the study had brought to light an interesting detail about MLKL. Three-dimensional images of its structure show that it is a “dead enzyme” unlike the other proteins in the signalling pathway. The researchers established that MLKL had to be “switched on” in order to trigger necroptosis. This means that the protein could provide a perfect target for treatments. Since it differs from virtually all other cell-signalling proteins, it would be easier to create highly specific drugs and limit potential side effects, Murphy pointed out.

The researchers are now attempting to determine what “switched on” MLKL looks like at the atomic level. Success in this undertaking will make it possible to start developing drugs that can block it, Silke added.