Review
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World J Biol Chem. May 26, 2010; 1(5): 181-187
Published online May 26, 2010. doi: 10.4331/wjbc.v1.i5.181
Physio-pathological roles of transglutaminase-catalyzed reactions
Mariangela Ricotta, Maura Iannuzzi, Giulia De Vivo, Vittorio Gentile
Mariangela Ricotta, Maura Iannuzzi, Giulia De Vivo, Vittorio Gentile, Department of Biochemistry and Biophysics, Medical School, Second University of Naples, via Costantinopoli 16, 80138 Napoli, Italy
Author contributions: Ricotta M and Iannuzzi M performed part of experiments; De Vivo G designed and performed part of experiments; Gentile V co-ordinated and performed experiments and wrote the paper.
Correspondence to: Vittorio Gentile, MD, PhD, Neurologist, Aggregate Professor of Biochemistry, Department of Biochemistry and Biophysics, Medical School, Second University of Naples, via Costantinopoli 16, 80138 Napoli, Italy. vittorio.gentile@unina2.it
Telephone: +39-81-5665870 Fax: +39-81-5665863
Received: April 24, 2010
Revised: May 4, 2010
Accepted: May 14, 2010
Published online: May 26, 2010
Abstract

Transglutaminases (TGs) are a large family of related and ubiquitous enzymes that catalyze post-translational modifications of proteins. The main activity of these enzymes is the cross-linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue 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 the absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. The TG enzymes are also capable of catalyzing other reactions important for cell viability. The distribution and the physiological roles of TG enzymes have been widely studied in numerous cell types and tissues and their roles in several diseases have begun to be identified. “Tissue” TG (TG2), a member of the TG family of enzymes, has definitely been shown to be involved in the molecular mechanisms responsible for a very widespread human pathology: i.e. celiac disease (CD). TG activity has also been hypothesized to be directly involved in the pathogenetic mechanisms responsible for several other human diseases, including neurodegenerative diseases, which are often associated with CD. Neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, supranuclear palsy, Huntington’s disease and other recently identified polyglutamine diseases, are characterized, in part, by aberrant cerebral TG activity and by increased cross-linked proteins in affected brains. In this review, we discuss the physio-pathological role of TG-catalyzed reactions, with particular interest in the molecular mechanisms that could involve these enzymes in the physio-pathological processes responsible for human neurodegenerative diseases.

Keywords: Transglutaminases, Post-translational-modifications of proteins, Celiac disease, Neurodegenerative diseases, Transglutaminase inhibitors