Possible roles of transglutaminases in molecular mechanisms responsible for cancer and human neurodegenerative diseases

  • Gabriella Misso | gabrymisso@yahoo.it Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
  • Nicola Gaetano Gatta Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
  • Mayra Rachele Zarone Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
  • Gaetano Cammarota Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
  • Anna Grimaldi Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
  • Vittorio Gentile Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.

Abstract

Transglutaminases are a family of Ca2+- dependent enzymes which catalyze posttranslational modifications of proteins. The main activity of these enzymes is the crosslinking 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 either 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, cancer and neurodegenerative diseases, such as Alzheimer’s Disease, Parkinson’s Disease, supranuclear palsy and Huntington’s Disease, are characterized in part by aberrant transglutaminase activity and by increased cross-linked proteins in affected tissues. This review describes 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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Published
2017-07-19
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Section
Review Articles
Keywords:
Transglutaminases, Post-translational modifications of proteins, Cancer, NFkB, Neurodegeneration
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How to Cite
Misso, G., Gatta, N. G., Zarone, M. R., Cammarota, G., Grimaldi, A., & Gentile, V. (2017). Possible roles of transglutaminases in molecular mechanisms responsible for cancer and human neurodegenerative diseases. Translational Medicine Reports, 1(2). https://doi.org/10.4081/tmr.6599