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

Nicola Gaetano Gatta; Rosaria Romano; Elenamaria Fioretti; Vittorio Gentile

doi:10.3934/molsci.2017.4.399

AIMS Molecular Science, 2017, 4(4): 399-414. doi: 10.3934/molsci.2017.4.399. Review Topical Section

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

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

1 Department of Biochemistry, Biophysics and General Pathology, University of Campania “Luigi Vanvitelli”, via Costantinopoli 16, 80138 Naples, Italy
2 Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, via Costantinopoli 16, 80138 Naples, Italy

Received: , Accepted: , Published:

Topical Section: Molecular Mechanisms of Neurodegenerative Diseases

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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 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.

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Keywords: transglutaminases; post-translational modifications of proteins; neurodegeneration; NF-kB; neuroinflammation

Citation: Nicola Gaetano Gatta, Rosaria Romano, Elenamaria Fioretti, Vittorio Gentile. Transglutaminase inhibition: possible therapeutic mechanisms to protect cells from death in neurological disorders. AIMS Molecular Science, 2017, 4(4): 399-414. doi: 10.3934/molsci.2017.4.399

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