Abstract
The hyaluronidases (HAases) are a group of less extensively studied glycosidases distributed throughout the animal kingdom and are popularly known as ‘spreading factors’. In recent years, HAases received much attention due to their ability to abruptly alter the hyaluronic acid (HA) homeostasis. HAases preferentially degrade HA, which is a megadalton acidic structural polysaccharide found exclusively in the extracellular matrix (ECM) of animals. The HA-HAase system has been suggested to participate in many pathophysiological conditions. The HA degradation in ECM, crack down the structural integrity with an eventual increased tissue permeability that is attributed for the spreading property. The spreading property has been widely accepted in functions including envenomation, acrosomal reaction/ovum fertilization, cancer progression, microbial pathogenesis such as wound infections, pneumonia, and other sepses like, bacteremia and meningitis. HA fragmentation has dual effects; generation of a wide molecular range bioactive oligosaccharides of angiogenic, pro-inflammatory, and immunostimulatory properties; and impairment in the reservoir capacity of ECM that holds metal ions, growth factors, cytokines and various enzymes for signal transduction. Hence, inhibition of HA degradation appears critical and imperative in HAase mediated pathological conditions. HAase inhibitors are thus potent regulators that maintain HA homeostasis and they might serve as anti-inflammatory, anti-aging, anti-microbial, anticancer and anti-venom/toxin and contraceptive agents. In addition, HAase inhibitors may serve as tools to understand several unexplained and complex functions of HAases in HA metabolism. Therefore, this review is expected to provide an integrated update as of 2008 on the HAase inhibitors and their possible role as therapeutics in the management of a wide range of pathological conditions.
Keywords: Hyaluronan, hyaluronidase inhibitors, bioactive molecules, extracellular matrix, flavonoids, synthetic molecules, microbial venoms, animal venoms
Current Medicinal Chemistry
Title: Hyaluronidase Inhibitors: A Biological and Therapeutic Perspective
Volume: 16 Issue: 18
Author(s): K. S. Girish, K. Kemparaju, S. Nagaraju and B. S. Vishwanath
Affiliation:
Keywords: Hyaluronan, hyaluronidase inhibitors, bioactive molecules, extracellular matrix, flavonoids, synthetic molecules, microbial venoms, animal venoms
Abstract: The hyaluronidases (HAases) are a group of less extensively studied glycosidases distributed throughout the animal kingdom and are popularly known as ‘spreading factors’. In recent years, HAases received much attention due to their ability to abruptly alter the hyaluronic acid (HA) homeostasis. HAases preferentially degrade HA, which is a megadalton acidic structural polysaccharide found exclusively in the extracellular matrix (ECM) of animals. The HA-HAase system has been suggested to participate in many pathophysiological conditions. The HA degradation in ECM, crack down the structural integrity with an eventual increased tissue permeability that is attributed for the spreading property. The spreading property has been widely accepted in functions including envenomation, acrosomal reaction/ovum fertilization, cancer progression, microbial pathogenesis such as wound infections, pneumonia, and other sepses like, bacteremia and meningitis. HA fragmentation has dual effects; generation of a wide molecular range bioactive oligosaccharides of angiogenic, pro-inflammatory, and immunostimulatory properties; and impairment in the reservoir capacity of ECM that holds metal ions, growth factors, cytokines and various enzymes for signal transduction. Hence, inhibition of HA degradation appears critical and imperative in HAase mediated pathological conditions. HAase inhibitors are thus potent regulators that maintain HA homeostasis and they might serve as anti-inflammatory, anti-aging, anti-microbial, anticancer and anti-venom/toxin and contraceptive agents. In addition, HAase inhibitors may serve as tools to understand several unexplained and complex functions of HAases in HA metabolism. Therefore, this review is expected to provide an integrated update as of 2008 on the HAase inhibitors and their possible role as therapeutics in the management of a wide range of pathological conditions.
Export Options
About this article
Cite this article as:
Girish S. K., Kemparaju K., Nagaraju S. and Vishwanath S. B., Hyaluronidase Inhibitors: A Biological and Therapeutic Perspective, Current Medicinal Chemistry 2009; 16 (18) . https://dx.doi.org/10.2174/092986709788453078
DOI https://dx.doi.org/10.2174/092986709788453078 |
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
-
Recent Insights into COVID-19 in Children and Clinical Recommendations
Current Pediatric Reviews Diagnostic Value of CRP, Procalcitonin, and Ferritin Levels in Cerebrospinal Fluid of Children with Meningitis
Central Nervous System Agents in Medicinal Chemistry In Vitro and In Vivo Modeling of Tuberculosis Drugs and its Impact on Optimization of Doses and Regimens
Current Pharmaceutical Design The Nun Study: Risk Factors for Pathology and Clinical-Pathologic Correlations
Current Alzheimer Research Toll-Like Receptors: Sensor Molecules for Detecting Damage to the Nervous System
Current Protein & Peptide Science P2Y Receptors: Focus on Structural, Pharmacological and Functional Aspects in the Brain
Current Medicinal Chemistry Structure-Activity Relationship of Dicoumarol Derivatives as anti- Staphylococcus aureus (Staph Infection) Agents
Anti-Infective Agents Proteins Involved in the Membrane Translocation of Lipopolysaccharide O Antigen
Mini-Reviews in Organic Chemistry Selection of Potential Pharmacological Targets in ALS Based on Whole- Genome Expression Profiling
Current Medicinal Chemistry Leveraging Public Private Partnerships to Innovate under Challenging Budget Times
Current Topics in Medicinal Chemistry Cranial Ultrasound - Optimizing Utility in the NICU
Current Pediatric Reviews Kynurenine Pathway in Schizophrenia: Pathophysiological and Therapeutic Aspects
Current Pharmaceutical Design Revolutionary Impact of Nanodrug Delivery on Neuroscience
Current Neuropharmacology Opportunities and Challenges for Host-Directed Therapies in Tuberculosis
Current Pharmaceutical Design Cefepime-Induced Neurotoxicity
Central Nervous System Agents in Medicinal Chemistry Serial Analysis of Gene Expression in Eukaryotic Pathogens
Infectious Disorders - Drug Targets Pharmacogenomics and Severe Infections: The Role of the Genomes of Both the Host and the Pathogen
Current Pharmacogenomics Targeting the Nucleus: An Overview of Auger-Electron Radionuclide Therapy
Current Drug Discovery Technologies West Nile Virus NS2B/NS3 Protease As An Antiviral Target
Current Medicinal Chemistry Biomedical Technologies for In Vitro Screening and Controlled Delivery of Neuroactive Compounds
Central Nervous System Agents in Medicinal Chemistry