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Transglutaminase-Catalyzed Post-Translational Modifications of Proteins in the Nervous System and their Possible Involvement in Neurodegenerative Diseases

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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.

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Keywords: Transglutaminases; neurodegenerative diseases; post-translational modifications of proteins; transglutaminase inhibitors

Document Type: Research Article

Publication date: 2008-10-01

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  • CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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