Transglutaminase-dependent formation of protein aggregates as possible biochemical mechanism for polyglutamine diseases.

Transglutaminases (Enzyme Commission 2.3.2.13) are a large family of enzymes that show the common capacity to catalyze cross-linking of protein substrates. Some members of this family of enzymes are also capable of catalyzing other reactions important for the cell life. The distribution and the role of these enzymes have been widely studied in numerous cell types and tissues, but only recently their expression and functions started to be investigated in the central nervous system. One of the main biochemical properties of the transglutaminase enzymes is to form large protein aggregates that are insoluble in all known protein detergents, such as urea, guanidinium, and sodium dodecyl sulfate. Recently, the transglutaminase activity has been hypothesized to be involved in the pathogenetic mechanisms responsible for the formation of cellular inclusions present in Huntington disease and in all the other polyglutamine (polyQ) diseases hitherto identified, such as spinobulbar muscular atrophy or Kennedy disease, spinocerebellar ataxias (SCA-1, SCA-2, SCA-3 or Machado-Joseph disease, SCA-6 and SCA-7) and dentatorubropallidoluysian atrophy. In this review we describe the biochemical properties of the transglutaminase enzymes and some recent findings about the physiopathological roles played by these enzymes in the central nervous system.