title: Molecular mechanisms responsible for the involvement of tissue transglutaminase in human diseases: Celiac Disease.
abstract: Tissue transglutaminase (tTG or TG2; E.C. 2.3.2.13) belongs to the transglutaminase family, a group of closely related enzymes that share the ability to catalyze the cross-linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate. tTG is a multifunctional enzyme since it is also capable of catalyzing other biochemical reactions. The distribution and physiological roles of tTG have been widely studied in numerous cell types and tissues, but only recently its role in human diseases has started to be clarified. For example, transglutaminase activity has been hypothesized to be involved in the pathogenetic mechanisms responsible for several human diseases, including neurodegenerative diseases, such as polyglutamine diseases hitherto identified. Among human diseases, a large and recent series of studies have clearly shown that the activity of the tTG is critical for a very diffuse human pathology known as Celiac Disease. This disease is due to intolerance to a food component, gliadin, and is characterized by a very complex clinical syndrome, including gastrointestinal pathological manifestations, often associated with extra-intestinal manifestations. Interestingly, a subset of celiac patients also develops certain neurological disorders. In this review we describe the roles played by tTG in the molecular mechanisms responsible for pathophysiology of Celiac Disease.
authors.affiliation: Department of Biochemistry and Biophysics, Medical School, Second University of Naples, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Amantea
authors.forename: Marisa
authors.initials: M
authors.lastname: Cammarano
authors.forename: Lucia
authors.initials: L
authors.lastname: Zefferino
authors.forename: Antonio
authors.initials: A
authors.lastname: Martin
authors.forename: Gennaro
authors.initials: G
authors.lastname: Romito
authors.forename: Mariapina
authors.initials: M
authors.lastname: Piccirillo
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gentile
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D002446:Celiac Disease / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000627:therapeutic use*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019636:Neurodegenerative Diseases / Q000473:pathology; D010455:Peptides / Q000737:chemistry; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011499:Protein Processing, Post-Translational; D011503:Transglutaminases / Q000627:therapeutic use*
chemical_list: D010455:Peptides; C097188:polyglutamine; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins