It was nine years ago that University of Maryland School of Medicine researchers discovered that a mysterious human protein called zonulin played a critical role in celiac disease and other autoimmune disorders, such as multiple sclerosis and diabetes.
Now, scientists have solved the mystery of zonulin's identity, putting a face to the name, in a sense. Scientists led by Alessio Fasano, M.D., have identified zonulin as a molecule in the human body called haptoglobin 2 precursor.
Pinpointing the precise molecule that makes up the mysterious protein will enable a more detailed and thorough study of zonulin and its relationship to a series of inflammatory disorders. The discovery was reported in a new study by Dr. Fasano, published the week of September 7, 2009 in the online version of the Proceedings of the National Academy of Sciences. Dr. Fasano is a professor of pediatrics, medicine and physiology and director of the Mucosal Biology Research Center and the Center for Celiac Research at the University of Maryland School of Medicine.
Haptoglobin is a molecule that has been known to scientists for many years. It was identified as a marker of inflammation in the body. Haptoglobin 1 is the original form of the haptoglobin molecule, and scientists believe it evolved 800 million years ago. Haptoglobin 2 is a permutation found only in humans. It's believed the mutation occurred in India about 2 million years ago, spreading gradually among increasing numbers of people throughout the world.
Dr. Fasano's study revealed that zonulin is the precursor molecule for haptoglobin 2 — that is, it is an immature molecule that matures into haptoglobin 2. It was previously believed that such precursor molecules served no purpose in the body other than to mature into the molecules they were destined to become. But Dr. Fasano's study identifies precursor haptoglobin 2 as the first precursor molecule that serves another function entirely — opening a gateway in the gut, or intestines, to let gluten in. People with celiac disease suffer from a sensitivity to gluten.
"While apes, monkeys and chimpanzees do not have haptoglobin 2, 80 percent of human beings have it," says Dr. Fasano. "Apes, monkeys and chimpanzees rarely develop autoimmune disorders. Human beings suffer from more than 70 different kinds of such conditions. We believe the presence of this pre-haptoglobin 2 is responsible for this difference between species."
"This molecule could be a critical missing piece of the puzzle to lead to a treatment for celiac disease, other autoimmune disorders and allergies and even cancer, all of which are related to an exaggerated production of zonulin/pre-haptoglobin 2 and to the loss of the protective barrier of cells lining the gut and other areas of the body, like the blood brain barrier," says Dr. Fasano.
"The only current treatment for celiac disease is cutting gluten from the diet, but we have confidence Dr. Fasano's work will someday bring further relief to these patients. Zonulin, with its functions in health and disease as outlined in Dr. Fasano's paper, could be the molecule of the century," says E. Albert Reece, M.D., Ph.D., M.B.A., dean of the School of Medicine, vice president for medical affairs of the University of Maryland and John Z. and Akiko K. Bowers Distinguished Professor. Dr. Fasano, as a physician scientist, fulfills two of the core missions of the University of Maryland School of Medicine: making basic science discoveries that can impact human health, and finding ways to translate those discoveries into treatments and diagnostic tools."
People who suffer from celiac disease have a sensitivity to gluten, a protein found in wheat, and suffer gastrointestinal distress and other serious symptoms when they eat it. In celiac patients, gluten generates an exaggerated release of zonulin that makes the gut more permeable to large molecules, including gluten. The permeable gut allows these molecules, such as gluten, access to the rest of the body. This triggers an autoimmune response in which a celiac patient's immune system identifies gluten as an intruder and responds with an attack targeting the intestine instead of the intruder. An inappropriately high level of production of zonulin also seems responsible for the passage through the intestine of intruders other than zonulin, including those related to conditions such as diabetes, multiple sclerosis and even allergies. Recently, other groups have reported elevated production of zonulin affecting the permeability of the blood brain barrier of patients suffering from brain cancer.
"We hope pre-haptoglobin 2 will be a door to a better understanding of not just celiac disease, but of several other devastating conditions that continue to affect the quality of life of millions of individuals," says Dr. Fasano. "This is quite a remarkable molecule that was just flying under the radar. We would have never have thought it would be the key. Now that we have identified this molecule, we are able to replicate it in the lab to use for research purposes. We hope to learn much more about it and its potential for treating and diagnosing celiac disease and other autoimmune conditions. This molecule has opened innumerable doors for our research."
Karen Warmkessel | EurekAlert!
Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania
The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction