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. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono- or bisubstituted /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. These enzymes are also capable of catalyzing other reactions important for cell viability. The distribution and the physiological roles of 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 Alzheimers disease (AD), Parkinsons disease (PD), supranuclear palsy, Huntingtons disease (HD) and the other recently identified polyglutamine diseases, and others. In this review we discuss the biological role of the transglutaminases in the nervous system, with particular interest in the molecular mechanisms, which could involve these enzymes in the pathophysiological processes responsible for human neurodegenerative diseases.
Keywords: Transglutaminases, Post-translational modifications of proteins, Neurodegenerative diseases, Transglutaminase inhibitors
Current Medicinal Chemistry
Title: Role of the Transglutaminase Enzymes in the Nervous System and their Possible Involvement in Neurodegenerative Diseases
Volume: 16 Issue: 36
Author(s): G. De Vivo, R. Di Lorenzo, M. Ricotta and V. Gentile
Affiliation:
Keywords: Transglutaminases, Post-translational modifications of proteins, Neurodegenerative diseases, Transglutaminase inhibitors
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. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono- or bisubstituted /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. These enzymes are also capable of catalyzing other reactions important for cell viability. The distribution and the physiological roles of 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 Alzheimers disease (AD), Parkinsons disease (PD), supranuclear palsy, Huntingtons disease (HD) and the other recently identified polyglutamine diseases, and others. In this review we discuss the biological role of the transglutaminases in the nervous system, with particular interest in the molecular mechanisms, which could involve these enzymes in the pathophysiological processes responsible for human neurodegenerative diseases.
Export Options
About this article
Cite this article as:
De Vivo G., Di Lorenzo R., Ricotta M. and Gentile V., Role of the Transglutaminase Enzymes in the Nervous System and their Possible Involvement in Neurodegenerative Diseases, Current Medicinal Chemistry 2009; 16 (36) . https://dx.doi.org/10.2174/092986709789909594
DOI https://dx.doi.org/10.2174/092986709789909594 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Structure and Functions of P-Glycoprotein
Current Medicinal Chemistry Fragile X Mental Retardation Protein: Many Partners and Multiple Targets for a Promiscuous Function
Current Genomics Aquaporins and Roles in Brain Health and Brain Injury
Mini-Reviews in Medicinal Chemistry Antimicrobial Activity of SPC13, New Antimicrobial Peptide Purified from Scolopendra polymorpha Venom
Anti-Infective Agents Bone Marrow-Derived Mesenchymal Stem Cells Contribute to the Reduction of Amyloid-β Deposits and the Improvement of Synaptic Transmission in a Mouse Model of Pre-Dementia Alzheimer’s Disease
Current Alzheimer Research Is a "Mitochondrial Psychiatry" in the Future? A Review
Current Psychiatry Reviews Brain Aging and Disorders of the Central Nervous System: Kynurenines and Drug Metabolism
Current Drug Metabolism Editorial [Hot Topic: Membrane Channels as Therapeutic Targets (Executive Editor: Jean-Claude Herve)]
Current Pharmaceutical Design Editorial Review 2015
Current Radiopharmaceuticals Recent Advances in the Modulation of Voltage-Gated Ion Channels for the Treatment of Epilepsy
Current Drug Targets - CNS & Neurological Disorders Editorial: Antiepileptic Drugs in Neurosurgical Practic
Current Pharmaceutical Design Characterization of a New Positive Allosteric Modulator of AMPA Receptors - PAM-43: Specific Binding of the Ligand and its Ability to Potentiate AMPAR Currents
Current Molecular Pharmacology Kainic Acid-Induced Neurotoxicity: Targeting Glial Responses and Glia-Derived Cytokines
Current Neuropharmacology Fibromyalgia: Mechanisms, Current Treatment and Animal Models
Current Pharmaceutical Biotechnology Editorial (Thematic Issue: Targeting Transporters for CNS Drug Delivery)
Current Pharmaceutical Design Autophagy Enhancer Carbamazepine Alleviates Memory Deficits and Cerebral Amyloid-β Pathology in a Mouse Model of Alzheimer's Disease
Current Alzheimer Research Preterm Birth and the Risk of Neurodevelopmental Disorders - Is There a Role for Epigenetic Dysregulation?
Current Genomics Drug Targets of Migraine and Neuropathy: Treatment of Hyperexcitability
CNS & Neurological Disorders - Drug Targets Neuroimaging of Non-Accidental Injury
Current Pediatric Reviews Neural Progenitors and HIV-1- Associated Central Nervous System Disease in Adults and Children
Current HIV Research