Abstract
Transglutaminases (TGases), a family of enzymes that catalyze the formation of ε-(γ-glutamyl)lysine isopeptide linkage, play an important physiological role in hemostasis, wound healing, assembly and remodeling of the extracellular matrix, cell signaling and apoptosis. Although many members of this class of enzymes have been known for decades, their role in various physiological and pathological processes is still a subject of substantial research and debate. Convincing evidence exists that TGases are involved in formation of cytotoxic proteinatious aggregates in Alzheimers, Huntingtons and other neurodegenerative diseases. However, it is not clear if elevated levels of TGases play a causative or protective role in several of these processes. Increased or defective TGase activity is a factor in cortical cataract formation, lamellar ichtyosis and fibrosis. TGase creates epitopes for the production of autoantibodies in celiac disease and possibly other autoimmune diseases. Another TGase, Factor XIIIa, is involved in the etiology of vascular diseases. Modulation of TGase activity through its selective inhibition may have therapeutic benefit in a wide variety of diseases. This paper will examine TGases as targets for the development of new therapeutics and review the progress in discovery of selective inhibitors of these enzymes.
Keywords: transglutaminase, factor xiii, thrombosis, neurodegenerative disease, celiac disease, inflammation, fibrosis and inhibitor
Mini-Reviews in Medicinal Chemistry
Title: Transglutaminases as Targets for Pharmacological Inhibition
Volume: 5 Issue: 3
Author(s): Jolanta M. Wodzinska
Affiliation:
Keywords: transglutaminase, factor xiii, thrombosis, neurodegenerative disease, celiac disease, inflammation, fibrosis and inhibitor
Abstract: Transglutaminases (TGases), a family of enzymes that catalyze the formation of ε-(γ-glutamyl)lysine isopeptide linkage, play an important physiological role in hemostasis, wound healing, assembly and remodeling of the extracellular matrix, cell signaling and apoptosis. Although many members of this class of enzymes have been known for decades, their role in various physiological and pathological processes is still a subject of substantial research and debate. Convincing evidence exists that TGases are involved in formation of cytotoxic proteinatious aggregates in Alzheimers, Huntingtons and other neurodegenerative diseases. However, it is not clear if elevated levels of TGases play a causative or protective role in several of these processes. Increased or defective TGase activity is a factor in cortical cataract formation, lamellar ichtyosis and fibrosis. TGase creates epitopes for the production of autoantibodies in celiac disease and possibly other autoimmune diseases. Another TGase, Factor XIIIa, is involved in the etiology of vascular diseases. Modulation of TGase activity through its selective inhibition may have therapeutic benefit in a wide variety of diseases. This paper will examine TGases as targets for the development of new therapeutics and review the progress in discovery of selective inhibitors of these enzymes.
Export Options
About this article
Cite this article as:
Wodzinska M. Jolanta, Transglutaminases as Targets for Pharmacological Inhibition, Mini-Reviews in Medicinal Chemistry 2005; 5 (3) . https://dx.doi.org/10.2174/1389557053175416
DOI https://dx.doi.org/10.2174/1389557053175416 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Drugs and mitochondria
Mitochondria play a central role in the life and death of cells. They are not merely the center for energy metabolism but are also the headquarters for different catabolic and anabolic processes, calcium fluxes, and various signaling pathways. Mitochondria maintain homeostasis in the cell by interacting with reactive oxygen-nitrogen species ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer’s, Parkinson’s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...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
Related Articles
-
Treatment of Choroidal Neovascularization in High Myopia
Current Drug Targets Impact of the CD40-CD40L Dyad in Alzheimers Disease
CNS & Neurological Disorders - Drug Targets Pharmacological Interventions on Asymmetric Dimethylarginine, a Clinical Marker of Vascular Disease
Current Medicinal Chemistry Unravling the Impact: Pulmonary Side Effects of Anti-seizure Medications
Current Respiratory Medicine Reviews Anti-Inflammatory Agents from Plants: Progress and Potential
Current Medicinal Chemistry Advanced Glycation: A Novel Outlook on Atherosclerosis
Current Pharmaceutical Design Pharmacophore and 3D QSAR Study of TGFβ Inhibitors
Letters in Drug Design & Discovery Obstructive Sleep Apnea and Cardiovascular Disease - A New Target for Treatment
Current Pharmaceutical Design Probing Cerebrovascular Alterations in Alzheimers Disease Using MRI: From Transgenic Models to Patients
Current Medical Imaging Effectiveness of Long-Term Macrolide Therapy in Cryptogenic Organising Pneumonia
Current Respiratory Medicine Reviews Perinatal Heart Programming: Long-term Consequences
Current Medicinal Chemistry Oxidative Stress and Cardiac Remodeling: An Updated Edge
Current Cardiology Reviews Aquaporins and Neurodegenerative Diseases
Current Neuropharmacology An Insight into the Recent Diabetes Trials: What is the Best Approach to Prevent Macrovascular and Microvascular Complications?
Current Diabetes Reviews High Sensitivity C-reactive Protein and Cardiovascular Risk Prediction
Current Pharmaceutical Analysis Hallmarks in the Therapeutic Approach of Aortic Aneurysms: The Main Contributors
Current Pharmaceutical Design Editorial [Hot Topic: Vascular Complications of Diabetes (Executive Editor: Olga I. Stenina)]
Current Pharmaceutical Design Phosphodiesterases as Therapeutic Targets for Huntington’s Disease
Current Pharmaceutical Design Stem Cells for Microenvironmental Modulation and Retinal Regeneration
Current Tissue Engineering (Discontinued) Mechanisms and Characteristics of Sulfonylureas and Glinides
Current Topics in Medicinal Chemistry