NewsWorldCSIC scientists investigate how to treat celiac disease -...

CSIC scientists investigate how to treat celiac disease – RTVE

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Scientists from the Higher Council for Scientific Research (CSIC) have discovered that a molecule could degrade the gliadin protein and the 33-mer peptide, one of the main triggers of celiac disease, they report in a note. The molecule studied in a study led by researchers from the Barcelona Institute of Molecular Biology (IBMB-CSIC) is neprosin, which is found naturally in the digestive fluid of the carnivorous plant Nepenthes ventrata. As revealed by the work led by the researcher F. Xavier Gomis-Rüth ​​and whose first authors are the researchers Laura del Amo-Maestro and Soraia Mendes, neprosin is a promising treatment option for celiac disease. The authors have deciphered the mechanism of action of the molecule, its structure, as well as its most relevant characteristics for a possible treatment of the disease. Possible development of prevention or treatmentCeliac disease is triggered by various prolamin-rich proteins found in cereals. When these proteins are digested in the stomach, they break down into smaller ones (peptides) that can be toxic. Among these peptides, one of the most important is 33-mer, which is a fragment of alpha-gliadin, a prolamin (plant glycoprotein) from wheat. The 33-mer peptide is able to resist gastric acids from the stomach and reach to the small intestine and, once there, it crosses the intestinal mucosa. In the case of people with celiac disease, the 33-mer binds with particular ease to an immune system receptor (the human leukocyte antigen or HLA), which triggers an autoimmune and inflammatory response that ends up causing a whole series of characteristic manifestations of celiac disease. the disease. The results of the teams from the Proteolysis Group of the IBMB-CSIC and the Autoimmunity, Immunonutrition and Tolerance group of the UB show that neprosin can degrade the 33-mer peptide before it reaches the intestine, with which it could prevent this inflammatory autoimmune response. Scientists have obtained recombinant cultures of human cells to obtain sufficient amounts of neprosin. They have identified and determined the mechanism of action of neprosin, as well as its ability to destroy gliadin and the 33-mer peptide. They have also resolved the three-dimensional structure and chemical mechanism of action of neprosin and established characteristics such as its thermal stability. , its pH profile, and its latency period, among others. Very important factors for a possible development of the prevention or treatment, until now non-existent, of the disease. The next step, verifying the potential “A promising pathway is molecules that destroy toxic peptides, and that can be administered orally, similar to the lactase tablets that people who are lactose intolerant take,” the scientists explain. “The studies we have carried out have allowed us to verify that neprosin has enormous potential to be developed as a medicine, since it is much more active in the extreme conditions of digestion in the stomach than other enzymes”, points out the CSIC researcher F Xavier Gomis-Rüth.“We are now going to move on to more specific tests to verify this potential before moving on to clinical trials and working with mutant molecules that may be even more efficient”, he adds.

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