Effective Degradation of Gluten and Its Fragments by Gluten-Specific Peptidases: A Review on Application for the Treatment of Patients with Gluten Sensitivity

Abstract

To date, there is no effective treatment for celiac disease (CD, gluten enteropathy), an autoimmune disease caused by gluten-containing food. Celiac patients are supported by a strict gluten-free diet (GFD). However, in some cases GFD does not negate gluten-induced symptoms. Many patients with CD, despite following such a diet, retain symptoms of active disease due to high sensitivity even to traces of gluten. In addition, strict adherence to GFD reduces the quality of life of patients, as often it is difficult to maintain in a professional or social environment. Various pharmacological treatments are being developed to complement GFD. One promising treatment is enzyme therapy, involving the intake of peptidases with food to digest immunogenic gluten peptides that are resistant to hydrolysis due to a high prevalence of proline and glutamine amino acids. This narrative review considers the features of the main proline/glutamine-rich proteins of cereals and the conditions that cause the symptoms of CD. In addition, we evaluate information about peptidases from various sources that can effectively break down these proteins and their immunogenic peptides, and analyze data on their activity and preliminary clinical trials. Thus far, the data suggest that enzyme therapy alone is not sufficient for the treatment of CD but can be used as a pharmacological supplement to GFD.

Recombinant Cathepsin L of Tribolium castaneum and Its Potential in the Hydrolysis of Immunogenic Gliadin Peptides

“…A convenient source of such enzymes can be digestive enzymes of representatives of the Tenebrionidae family, whose main diet includes gluten proteins rich in proline and glutamine, particularly the stored product insect pest T. castaneum. It should be noted that, whereas proline-specific peptidases that cleave bonds formed by proline are relatively well studied [19,20], only a limited range of glutamine-specific peptidases are known [28]. Therefore, we evaluated the activity of T. castaneum cathepsin L as a prospective candidate for the development of an effective pharmaceutical for the therapy of celiac disease and other gluten intolerances.…”

“…They contain 30-50% glutamine residues and 10-30% proline residues [18]. Recent studies attempt to identify the enzymes that can effectively hydrolyze immunogenic prolamin peptides so that they can be used for the enzymatic therapy of celiac disease [19][20][21][22][23][24][25][26][27][28]. In our laboratory, the main T. castaneum digestive cathepsins L NP_001164001 (TcCathL1) and NP_001164314 (TcCathL2) were isolated, and their ability to cleave the fluorogenic analogues of immunogenic prolamin peptides was shown [11], which allows them to be considered as potential candidates for the treatment of celiac disease.…”

Biochemical Characterisation and Structure Determination of a Novel Cold-Active Proline Iminopeptidase from the Psychrophilic Yeast, Glaciozyma antarctica PI12

“…In pharmaceutical and medical applications, PIP can enhance the degradation of gluten, which may cause serious problems for patients suffering from celiac disease. Celiac disease is an intestinal disorder due to an uncontrolled immune response, which is caused by gluten proteins that are resistant to proteolytic degradation within the gastrointestinal tract [18].…”

Proteomic View on Gluten Structure in Different Types of Flour and Bread Samples by Using Bottom Up Proteomics and Ft-Ir Spectroscopy

“…Gluten term refers to a protein complex contains gliadins (prolamins) and glutenins as major subunits. Both of these proteins have high proline and glutamine aminoacids, which are responsible from Coeliac Disease (Celiac Disease, CD) (Caminero et al, 2012;Dunaevsky et al, 2021). Gliadins which play a key role in CD contain around 40% glutamine and around 14% proline (Dziuba et al, 2014).…”