Andrea Parente, Nicola Gaetano Gatta, Maria Battipaglia, Filomena Capolongo, Vittorio Gentile*
Transglutaminases are a family of Ca2+-dependent enzymes which catalyze post-translational modifications of proteins.
The main activity of these enzymes is the cross-linking of glutaminyl residues of a protein/peptide substrate to lysyl
residues of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may
include monoamines or polyamines (to form mono- or bi-substituted/crosslinked adducts) or –OH groups (to form ester
linkages). In absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl
residue. Transglutaminase activity has been suggested to be involved in molecular mechanisms responsible for both
physiological or pathological processes. In particular, transglutaminase activity has been shown to be responsible for
human autoimmune diseases, and Celiac Disease is just one of them. Interestingly, neurodegenerative diseases, such as
Alzheimer’s Disease, Parkinson’s Disease, supranuclear palsy, Huntington’s Disease and other polyglutamine diseases, are
characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected
brains. Here we describe the possible molecular be responsible for such diseases and the possible use of transglutaminase
inhibitors for patients with diseases mechanisms by which these enzymes could characterized by aberrant transglutaminase
activity.
