Scientists Have Found an ‘Off Switch’ For Celiac’s Disease

❝Celiac disease is an autoimmune disorder that affects by some estimates nearly 1 in 100 people. Celiac disease symptoms are triggered by gluten, a protein found in wheat and related plants, but gluten doesn’t act alone to cause the digestive symptoms that patients suffer. Rather, gluten induces an overactive immune response when it’s modified by the enzyme transglutaminase 2, or TG2, in the small intestine. New research published in the Feb. 23 issue of the Journal of Biological Chemistry identifies an enzyme that turns off TG2, potentially paving the way for new treatments for celiac disease.

“Currently, therapies to treat people with celiac disease are lacking. The best approach right now is just a strict adherence to a lifelong gluten-free diet,” said Michael Yi, a chemical engineering graduate student at Stanford University who led the new study. “Perhaps the reason behind this is our relatively poor understanding of TG2.”

The biochemistry of how TG2 interacts with gluten and induces an immune response has been well studied, but more basic mysteries remain, for example how TG2 behaves in people without celiac disease. Chaitan Khosla, the professor at Stanford and director of Stanford Chemistry, has conducted several studies showing that TG2 can be active or inactive, depending on the forming or breaking of a specific chemical bond, called a disulfide bond, between two amino acids in the enzyme.

Khosla said: “When it became clear that even though the protein was abundant, its activity was nonexistent in a healthy organ, the question became ‘What turns the protein on, and then what turns the protein off?’”

In 2011, Khosla’s team identified the enzyme that activates TG2 by breaking its disulfide bond. In the new paper, the researchers performed experiments in cell cultures and found an enzyme that re-forms this bond, inactivating TG2. This enzyme, ERp57, is mainly known for helping fold proteins inside the cell. When it turns off TG2, it does so outside of cells, raising more questions about its functions in healthy people.
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Tags: Celiac’s Disease + gluten + gluten-free diet + Michael Yi