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Transglutaminase-catalyzed post-translational modifications of proteins in the nervous system and their possible involvement in neurodegenerative diseases.

Abstract
Transglutaminases are a large family of related and ubiquitous enzymes which 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 reactions important for the cell viability. The distribution and the physiological roles of the human transglutaminases have been widely studied in numerous cell types and tissues and their roles in several diseases have begun to be identified. Recently, "tissue" transglutaminase (TG2) has been shown to be involved in the molecular mechanisms responsible for a very widespread human pathology, Celiac Disease (CD). Transglutaminase activity has also been hypothesized to be directly involved in the pathogenetic mechanisms responsible for several human neurodegenerative diseases, which are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains, such as Alzheimer's disease (AD), Parkinson's disease (PD), supranuclear palsy, Huntington's disease (HD) and other recently identified polyglutamine diseases. In this review we discuss the biochemistry of the transglutaminases, with particular reference to the molecular mechanisms that could be involved in the physiopathological processes responsible for these human neurodegenerative diseases.
AuthorsG De Vivo, V Gentile
JournalCNS & neurological disorders drug targets (CNS Neurol Disord Drug Targets) Vol. 7 Issue 4 Pg. 370-5 (Oct 2008) ISSN: 1996-3181 [Electronic] United Arab Emirates
PMID18991665 (Publication Type: Journal Article, Review)
Chemical References
  • Nerve Tissue Proteins
  • Glutamine
  • Transglutaminases
  • transglutaminase 1
Topics
  • Animals
  • Brain (enzymology, physiopathology)
  • Brain Chemistry (genetics)
  • Genetic Predisposition to Disease (genetics)
  • Glutamine (metabolism)
  • Humans
  • Inclusion Bodies (genetics, metabolism)
  • Nerve Tissue Proteins (genetics, metabolism)
  • Neurodegenerative Diseases (enzymology, genetics, physiopathology)
  • Protein Processing, Post-Translational (genetics)
  • Transglutaminases (genetics, metabolism)
  • Trinucleotide Repeat Expansion (genetics)

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