title: Transglutaminase as a therapeutic target for celiac disease.
abstract: BACKGROUND
  The only current treatment for celiac disease is a strict gluten-free diet. The ubiquitous presence of gluten in groceries, however, makes the diet burdensome and difficult to maintain, and alternative treatment options are thus needed. Here, the important role of transglutaminase 2 (TG2) in the pathogenesis of celiac disease makes it an attractive target for drug development.
  
  
  METHODS
  The present paper gives an overview of TG2 and addresses its significance in the pathogenesis of celiac disease. Moreover, the article summarizes preclinical studies performed with TG2 inhibitors and scrutinizes issues related to this therapeutic approach.
  
  
  CONCLUSIONS
  Activation of TG2 in the intestinal mucosa is central in celiac disease pathogenesis and researchers have therefore suggested TG2 inhibitors as a potential therapeutic approach. However, a prerequisite for such a drug is that it should be specific for TG2 and not affect the activity of other members of the transglutaminase family. Such compounds have already been introduced and tested in vitro, but a major obstacle to further development is the lack of a well-defined animal model for celiac disease. Nonetheless, with encouraging results in preclinical studies clinical trials with TG2 inhibitors are eagerly awaited.
authors.affiliation: Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital , Tampere , Finland +358 50 3186306; +358 3 3641369 ; katri.lindfors@uta.fi.
authors.forename: Ana-Marija
authors.initials: AM
authors.lastname: Sulic
authors.forename: Kalle
authors.initials: K
authors.lastname: Kurppa
authors.forename: Tiina
authors.initials: T
authors.lastname: Rauhavirta
authors.forename: Katri
authors.initials: K
authors.lastname: Kaukinen
authors.forename: Katri
authors.initials: K
authors.lastname: Lindfors
mesh_terms: D000818:Animals; D002446:Celiac Disease / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D055050:Diet, Gluten-Free; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D058990:Molecular Targeted Therapy; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: celiac disease; drug; gluten; inhibitor; small-bowel; transglutaminase