Tissue transglutaminase and coeliac disease pathogenesis: potential molecular mechanisms for other human diseases

Coeliac disease (CD) is one of the most common food intolerances described in the western population. The main food agent that provokes the strong and diffuse clinical symptoms has been known for several years to be gliadin, a protein present in a very large number of human foods derived from vegetables. Only recently, some biochemical and immunological aspects of this very common disease have been clarified, and tissue transglutaminase, a multifunctional and ubiquitous enzyme, has been identified as one of the major factors. This enzyme, through its catalytic activities, produces the main biochemical and immunological effects observed in patients affected by this disease. The aim of this review is to summarize the most recent findings concerning the relationships between the biochemical properties of tissue transglutaminase and the basic molecular mechanisms responsible for CD. In addition, we present some frequent clinical associations of CD with other human diseases, with particular reference to neuropsychiatric disorders. Possible molecular links between CD, neuropsychiatric disorders and biochemical activities of transglutaminase enzymes are discussed.