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Type 2 transglutaminase in neurodegenerative diseases: the mitochondrial connection.

Abstract
"Tissue" or type 2 Transglutaminase (TG2) is a peculiar multifunctional enzyme able to catalyse Ca(2+)-dependent post-translational modification of proteins, by establishing covalent bonds between peptide-bound glutamine residues and either lysine residues or mono- and poly-amines. In addition, it may act also as a G protein in transmembrane signalling, as a kinase, as a protein disulphide isomerase and as a cell surface adhesion mediator. The vast array of biochemical functions exerted by TG2 characterises and distinguishes it from all the other members of the transglutaminase family. Multiple lines of evidence suggest an involvement of the enzyme in neurodegenerative diseases, such as Huntington's (HD) and Parkinson (PD), and that its inhibition, either via drug treatments or genetic approaches, might be beneficial for the treatment of these syndromes. This review will exploit the recent developments in the comprehension of the role played by type 2 transglutaminase in eukaryotic cells, focusing on the role exerted by TG2 on mitochondrial physiology and on the regulation of cell death pathways at the basis of neurodegenerative diseases.
AuthorsWalter Malorni, Maria Grazia Farrace, Carlo Rodolfo, Mauro Piacentini
JournalCurrent pharmaceutical design (Curr Pharm Des) Vol. 14 Issue 3 Pg. 278-88 ( 2008) ISSN: 1873-4286 [Electronic] United Arab Emirates
PMID18220838 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins
Topics
  • Animals
  • Autophagy (physiology)
  • Cell Death (physiology)
  • Cell Survival (physiology)
  • Drug Delivery Systems
  • Eukaryotic Cells (metabolism)
  • GTP-Binding Proteins (metabolism)
  • Gene Expression Regulation, Enzymologic (physiology)
  • Humans
  • Mitochondria (enzymology, physiology)
  • Neurodegenerative Diseases (enzymology, physiopathology)
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases (metabolism)

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