FEB 07, 2018 6:23 AM PST

NOD2 Pathway Linked to Crohn's Disease and Multiple Sclerosis

WRITTEN BY: Kara Marker

Defects in the body at the molecular level could at least partially explain why inflammatory diseases like Crohn’s disease, multiple sclerosis (MS), and potentially others develop. From the Walter and Eliza Hall Institute, scientists lead the charge on identifying and addressing these molecular defects.

Photomicrograph of a demyelinating MS-Lesion. Credit: Wikimedia user Marvin 101

In a new Cell Reports study, regulatory defects in an immune pathway called “NOD2” are to blame for mounting an unnecessary immune response. These defects prevent NOD2 from successfully controlling inflammation. In a situation where NOD2 is functioning normally, components of this pathway work together to discover and deal with invading microbes, like bacteria, by releasing inflammatory signals to thwart the invasion. In the context of Crohn’s or MS, the NOD2 pathway mistakenly continues to release inflammatory signals even when there is no longer a bacterial invasion to warrant it.

A protein called xIAP initiates the release of inflammatory signals, making it a clear candidate for drugs to treat Crohn’s and MS. However, xIAP also completes other functions in the cell apart from sparking the inflammatory response. And after xIAP initiates the response, there’s still more components of the NOD2 pathway that keep the response going.

“Once the NOD2 pathway trigger is initiated, the cells need a second, amplifying step to complete a full-strength immune response,” explained one of the study’s lead researchers, Che Stafford.

"Inflammation occurs when our immune cells release inflammatory messengers, or cytokines, which is a normal response to disease,” explained another lead researcher, Dr. Ueli Nachbur. “However when too many cytokines are produced, inflammation can get out-of-control and damage our own body - a hallmark of inflammatory diseases.”

Identifying the initiators - like xIAP - and enhancers of the NOD2 pathway responsible for inflammation could lead to discovering new drug options to treat conditions like Crohn’s or MS, where the inflammatory reaction goes wrong. Essentially, researchers can learn to manually “turn off” inflammation when there is no real bacterial threat and the inflammatory messengers are only causing damage to the body’s own cells.

It may be difficult to consider xIAP as a drug target candidate, as researchers don’t want to disturb its other roles in the cell not related to the inflammatory response in Crohn’s and MS.

"Chronic inflammatory conditions such as Crohn's disease and multiple sclerosis have a very significant impact to people's lives and new, targeted treatments are urgently needed,” Nachbur said. “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.”

Crohn’s disease is a type of inflammatory bowel disease that affects the gastrointestinal tract. Multiple sclerosis is a disease characterized by T cells of the immune system attacking the myelin sheath, the protective layer of insulation that surrounds nerves. When nerve signals are damaged due to inadequate insulation, various symptoms can occur: muscle spasms, vision loss, cognitive changes, and more.

Source: Walter and Eliza Hall Institute

About the Author
  • I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
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