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Master Regulator of the Faulty Inflammation Signaling in MS Identified by Australian Researchers

February 14, 2018

The master regulator of the immune response signaling pathway which is out of sync in multiple sclerosis as well as other inflammatory diseases has been identified by Australian researchers.

The team said the lynchpin in the process is the xIAP protein and their discovery that it triggers the NOD2 pathway’s faulty inflammation signaling shows promise for new MS therapies.

While protein NOD2 helps to control the signaling pathway, the team stated that xIAP plays a larger role.

Defects in the signaling pathway can cause diseases known for their uncontrolled inflammation like MS and Crohn’s.

When working as it should, the NOD2 pathway detects intruders such as bacteria, which triggers the release of inflammatory signals to fight the infection. This ends up defecting the pathway’s control system lead to immune cells that continue to generate inflammation after an infection is cleared, this ultimately results in a chronic inflammatory disease.

Ueli Nachbur of the Walter and Eliza Hall Institute of Medical Research explained how inflammation occurs when the immune cells release cytokines—a typical response to disease. However, he said “When too many cytokines are produced, inflammation can get out of control and damage our own body—a hallmark of inflammatory diseases.”

Researchers determined the xIAP protein “was the key to initiating the inflammatory response in these cells.” It was also found that the cells needed a second, amplifying step in order to complete a full-strength immune response once the NOD2’s pathway was triggered.

The team said that identifying both what triggers the inflammation signaling and what strengthens it was very necessary in order to lay down the groundwork for a therapy.

“Targeting key components of the NOD2 pathway shows promise as a way of switching off ongoing inflammation associated with diseases such as Crohn’s disease and multiple sclerosis,” Said the study’s first author, Che Stafford. The team also used preclinical-trial studies in 2015 to show “that blocking a different protein in the NOD2 pathway could halt inflammation, and was able to halt the progression of multiple sclerosis,” he said. “So it is very exciting to identify other potential targets for treating these diseases.”

Although it is a “tricky target for treating inflammatory diseases,” according to Nachbur, since xIAP has other tolls in the cell, like regulation of cell death. “However these new discoveries provide us with vital information to develop new treatment strategies that could lead to a safe and effective way of switching off inflammation for treating disease.”

https://multiplesclerosisnewstoday.com/2018/02/12/researchers-identify-master-regulator-of-inflammation-pathway-that-is-faulty-in-ms/