Abstract
Coeliac disease is a multifactorial disease characterized by a dysregulated immune response to ingested wheat gluten and related cereal proteins. With an incidence of about 1% of the general population, it is considered the most common food intolerance disorder. The mainstay of coeliac disease treatment is strict lifelong adherence to a gluten-free diet. Elimination of gluten and related proteins from the diet leads to clinical and histological improvement. However, some patients do not respond to dietary therapy and others have poor dietary compliance. This has prompted the search for a therapy alternative to a gluten-free diet. Tissue transglutaminase is a crucial factor in coeliac disease because it promotes the gluten-specific T-cell response and is also the target of the autoimmune response. Tissue transglutaminase induces changes in gluten, which in turn, cause the generation of a series of gluten peptides that bind to HLA-DQ2 or DQ8 molecules with high affinity. The resulting HLA-DQ2 (DQ8)-gluten peptide interaction triggers the proinflammatory T cell response. Tissue transglutaminase is also involved in other non-T-cell-mediated biological activities of gliadin peptides. For these reasons, tissue transglutaminase is a potential target for therapeutic intervention. In this paper we review the state-of-the-art of tissue transglutaminase inhibition, and examine known and new-generation inhibitors and their activity in in vitro and in vivo models. We also examine their potential as therapeutic tools for coeliac disease.
Keywords: Coeliac disease, tissue transglutaminase, gliadin, intestinal immunity, transglutaminase inhibitors
Current Medicinal Chemistry
Title: New Therapeutic Strategies for Coeliac Disease: Tissue Transglutaminase as a Target
Volume: 14 Issue: 24
Author(s): Carla Esposito, Ivana Caputo, Riccardo Troncone, Carla Esposito, Ivana Caputo and Riccardo Troncone
Affiliation:
Keywords: Coeliac disease, tissue transglutaminase, gliadin, intestinal immunity, transglutaminase inhibitors
Abstract: Coeliac disease is a multifactorial disease characterized by a dysregulated immune response to ingested wheat gluten and related cereal proteins. With an incidence of about 1% of the general population, it is considered the most common food intolerance disorder. The mainstay of coeliac disease treatment is strict lifelong adherence to a gluten-free diet. Elimination of gluten and related proteins from the diet leads to clinical and histological improvement. However, some patients do not respond to dietary therapy and others have poor dietary compliance. This has prompted the search for a therapy alternative to a gluten-free diet. Tissue transglutaminase is a crucial factor in coeliac disease because it promotes the gluten-specific T-cell response and is also the target of the autoimmune response. Tissue transglutaminase induces changes in gluten, which in turn, cause the generation of a series of gluten peptides that bind to HLA-DQ2 or DQ8 molecules with high affinity. The resulting HLA-DQ2 (DQ8)-gluten peptide interaction triggers the proinflammatory T cell response. Tissue transglutaminase is also involved in other non-T-cell-mediated biological activities of gliadin peptides. For these reasons, tissue transglutaminase is a potential target for therapeutic intervention. In this paper we review the state-of-the-art of tissue transglutaminase inhibition, and examine known and new-generation inhibitors and their activity in in vitro and in vivo models. We also examine their potential as therapeutic tools for coeliac disease.
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Esposito Carla, Caputo Ivana, Troncone Riccardo, Esposito Carla, Caputo Ivana and Troncone Riccardo, New Therapeutic Strategies for Coeliac Disease: Tissue Transglutaminase as a Target, Current Medicinal Chemistry 2007; 14 (24) . https://dx.doi.org/10.2174/092986707782023343
DOI https://dx.doi.org/10.2174/092986707782023343 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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