FEB 25, 2018 12:54 PM PST

Switching Off Celiac Disease

WRITTEN BY: Carmen Leitch

While gluten-free foods seem like a food trend to some, for others they are a medical necessity. Gluten triggers symptoms in people with celiac disease, an autoimmune disorder impacting around one in 100 people. In those with the disorder, gluten causes an overactive immune response after being modified in the small intestine by an enzyme called TG2, transglutaminase 2. Reporting in the Journal of Biological Chemistry, the researchers have discovered another enzyme that can inactivate TG2, and may help create celiac disease therapeutics.  

People with celiac disease cannot have wheat, which will trigger their symptoms. / Image credit: Pexels

"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," explained the study leader, Michael Yi, a chemical engineering graduate student at Stanford University. "Perhaps the reason behind this is our relatively poor understanding of TG2."

While it’s well known that gluten and TG2 interact to cause an immune response, and their interaction has been investigated, there are unanswered questions, like what TG2 does in the intestines of healthy people.

The director of Stanford Chemistry, Engineering & Medicine for Human Health, Professor Chaitan Khosla, oversaw the new work and has already led several studies indicating that TG2 is either active or inactive, depending on whether a disulfide bond in the enzyme is formed or broken.

"Though there's a lot of transglutaminase 2 protein in the (small intestine), it's all inactive," Khosla explained. "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?'" Several years ago, Khosla's team found the enzyme that breaks the disulfide bond, activating TG2. Now, the researchers conducted experiments that identified the enzyme that recreates that bond and turns off TG2 - ERp57. That enzyme has been understood to help fold cellular proteins inside of cells. But when it inactivates TG2, it functions outside of cells, raising other questions.

"Nobody really understands how (Erp57) gets outside the cell," Khosla noted. "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."

Now, TG2 is the first protein we know of with a reversible disulfide bond that acts as an on/off switch. "This is a very different kind of on-and-off chemistry than the kind that medicinal chemists would (typically) use," Khosla explained.

Now the team is building on their findings; they want to know if any FDA approved drugs already exist that can act on this switch. Previous work has suggested that low levels of TG2 don’t harm mice. Stopping TG2 may be a way to treat those with celiac disease, so they don’t have to follow a restrictive diet forever.

 

Sources: AAAS/Eurekalert! Via American Society for Biochemistry and Molecular Biology, Journal of Biological Chemistry

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
AUG 13, 2018
Microbiology
AUG 13, 2018
Insight Into the Origins of Junk DNA - From Koalas
The human genome isn't only genes. There's also long, repetitive sequences with an unknown function and origin....
AUG 23, 2018
Microbiology
AUG 23, 2018
Environmental Nanoparticles May be Harming Cells
Researchers suggest that we take time to learn more about the synthetic chemicals we're releasing into the environment....
SEP 10, 2018
Genetics & Genomics
SEP 10, 2018
In Autism, Background Mutations can Impact Disease Severity
While people are made from the same genes, small changes in those genes can have an impact on our biology....
SEP 24, 2018
Genetics & Genomics
SEP 24, 2018
Towards a Blood Test for Drowsy Driving
Driving is an everyday activity for many people around the world, and it comes with serious risks....
SEP 25, 2018
Health & Medicine
SEP 25, 2018
Can Cleaning Products Impact Childhood Obesity?
While many parents are cautious about the cleaning products they use around the house because small children could ingest them and become ill, most parents...
OCT 04, 2018
Videos
OCT 04, 2018
Zebrafish as Metastatic Cancer Model
Another Koch Institute Image Award winner from 2018 is presented in this video from MIT....
Loading Comments...