Possible pathophysiological roles of transglutaminase-catalyzed reactions in the pathogenesis of human neurodegenerative diseases

Enrica Serretiello; Martina Iannaccone; Federica Titta; Nicola G. Gatta; Vittorio Gentile; Enrica Serretiello; Martina Iannaccone; Federica Titta; Nicola G. Gatta; Vittorio Gentile

doi:10.3934/biophy.2015.4.441

AIMS Biophysics

2015, Volume 2, Issue 4: 441-457. doi: 10.3934/biophy.2015.4.441

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Possible pathophysiological roles of transglutaminase-catalyzed reactions in the pathogenesis of human neurodegenerative diseases

Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, via Costantinopoli 16, 80138 Naples, Italy

Received: 29 May 2015 Accepted: 28 August 2015 Published: 06 September 2015

Transglutaminases (TG, E.C. 2.3.2.13) are related and ubiquitous enzymes that catalyze the cross linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate. These enzymes are also capable of catalyzing other post-translational reactions important for cell life. The distribution and the physiological roles of human TGs have been widely studied in numerous cell types and tissues and recently their roles in several diseases have begun to be identified. It has been hypothesized that transglutaminase activity is directly involved in the pathogenetic mechanisms responsible for several human diseases. In particular, tissue TG (tTG, TG2), a member of the TG enzyme family, has been recently shown to be involved in the molecular mechanisms responsible for a very widespread human pathology, Celiac Disease (CD), one of the most common food intolerances described in the western population. The main food agent that provokes the strong and diffuse clinical symptoms has been known for several years to be gliadin, a protein present in a very large number of human foods derived from vegetables. Recently, some biochemical and immunological aspects of this very common disease have been clarified, and “tissue” transglutaminase, a multifunctional and ubiquitous enzyme, has been identified as one of the major factors. The aim of this review is to summarize the most recent findings concerning the relationships between the biochemical properties of the transglutaminase activity and the basic molecular mechanisms responsible for some human diseases, with particular reference to neuropsychiatric disorders. Possible molecular links between CD and neuropsychiatric disorders, and the use of transglutaminase inhibitors are also discussed.
- transglutaminases,
- post-translational modifications of proteins,
- celiac disease,
- neurodegenerative diseases,
- transglutaminase inhibitors,
- cystamine
Citation: Enrica Serretiello, Martina Iannaccone, Federica Titta, Nicola G. Gatta, Vittorio Gentile. Possible pathophysiological roles of transglutaminase-catalyzed reactions in the pathogenesis of human neurodegenerative diseases[J]. AIMS Biophysics, 2015, 2(4): 441-457. doi: 10.3934/biophy.2015.4.441

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Abstract

Transglutaminases (TG, E.C. 2.3.2.13) are related and ubiquitous enzymes that catalyze the cross linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate. These enzymes are also capable of catalyzing other post-translational reactions important for cell life. The distribution and the physiological roles of human TGs have been widely studied in numerous cell types and tissues and recently their roles in several diseases have begun to be identified. It has been hypothesized that transglutaminase activity is directly involved in the pathogenetic mechanisms responsible for several human diseases. In particular, tissue TG (tTG, TG2), a member of the TG enzyme family, has been recently shown to be involved in the molecular mechanisms responsible for a very widespread human pathology, Celiac Disease (CD), one of the most common food intolerances described in the western population. The main food agent that provokes the strong and diffuse clinical symptoms has been known for several years to be gliadin, a protein present in a very large number of human foods derived from vegetables. Recently, some biochemical and immunological aspects of this very common disease have been clarified, and “tissue” transglutaminase, a multifunctional and ubiquitous enzyme, has been identified as one of the major factors. The aim of this review is to summarize the most recent findings concerning the relationships between the biochemical properties of the transglutaminase activity and the basic molecular mechanisms responsible for some human diseases, with particular reference to neuropsychiatric disorders. Possible molecular links between CD and neuropsychiatric disorders, and the use of transglutaminase inhibitors are also discussed.

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