Review Article

Transglutaminase inhibition: possible therapeutic mechanisms to protect cells from death in neurological disorders

Vittorio Gentile*, Elenamaria Fioretti, Nicola Gaetano Gatta and Rosaria Romano

Published: 25 July, 2017 | Volume 1 - Issue 1 | Pages: 026-038

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 and 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 mechanisms by which these enzymes could be responsible for such diseases and the possible use of transglutaminase inhibitors for patients with diseases characterized by aberrant transglutaminase activity.

Read Full Article HTML DOI: 10.29328/journal.hjbm.1001004 Cite this Article Read Full Article PDF


Transglutaminases; Post-translational Modifications of Proteins; Neurodegeneration; NF-kB; Neuroinflammation


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