Researchers at Stanford University may have found a chemical “switch” that, if targeted, may stop celiac disease. The findings were published in the Journal of Biological Chemistry.
This amounts to at least 3 million U.S. citizens who live with the disease, most of whom have not been formally diagnosed with the condition.
Symptoms of celiac disease are triggered by the consumption of gluten, a protein often found in wheat, barley, and rye and some medicines, vitamins, and cosmetic products such as lip balms.
Currently, there are no therapies for celiac disease. Once diagnosed, the common approach is to simply stick to a gluten-free diet.
New research, however, brings us closer to finding such therapies; a chemical “switch” has been identified by scientists led by Chaitan Khosla, a professor at Stanford University in California.
It is known that the mechanism behind celiac disease involves an enzyme called transglutaminase 2 (TG2), which regulates gluten inside the small intestine. It causes an autoimmune response — or one wherein the immune system
First study author Michael Yi — a chemical engineering graduate student at Stanford University — hypothesized, together with his colleagues, that a poor understanding of TG2 may be the reason why there is no treatment for celiac disease yet.
So, they set out to investigate this enzyme more closely. Specifically, they wanted to see how TG2 behaves in healthy people. To do so, the scientists built on existing studies, which revealed that TG2 can be activated or deactivated by a certain chemical bond.
Prof. Khosla explains that in a healthy small intestine, even though TG2 is very abundant, it is inactive.
“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?'” says Prof. Khosla.
In a 2012
The previous study by Prof. Khosla and team found that breaking a chemical bond called a disulfide bond activates TG2. A disulfide bond is “a single covalent bond between the sulfur atoms to two amino acids.”
In this new paper, Prof. Khosla and team found another enzyme that recreates the disulfide bond, thereby deactivating TG2.
The enzyme — which is called ERp57 — normally helps proteins to “fold,” or gain their functional structure inside a cell.
But the cell culture experiments conducted by Prof. Khosla and team revealed that ERp57 switches off TG2 outside the cell. According to the researchers, this raises questions about how ERp57 works in healthy people.
“Nobody really understands,” explains Prof. Khosla, “how (Erp57) gets outside the cell. The general thinking is that it’s exported from the cell in small quantities; this particular observation suggests that it actually does have a biological role outside the cell.”
The researchers have now started to look into existing drugs that may be able to target this newly discovered “switch.”