Abstract
Microbial as well as endogenous nucleic acids are recognized by a group of endosomal Toll-like receptors TLR3, TLR7, TLR8 and TLR9. Recent discoveries significantly improved our understanding of molecular mechanism of their activation and their physiological role. Those include recognition of dsRNA through two nucleic acid binding sites of TLR3 ectodomain, activation of TLR9 by phosphodiester backbone of ssDNA, independent of the nucleotide sequence and phosphorothioate modified bonds, and the role of proteolysis in activation of TLR9. In addition, proteins that chaperone nucleic acids, such as HMGB1 or LL-37, have been described to mediate TLR activation. There is growing evidence that supports involvement of endosomal TLRs in a number of autoimmune diseases, suggesting a therapeutic potential of immunomodulatory endosomal TLR ligands. So far, inhibitory nucleic acids against TLR7, TLR8 and TLR9 as well as small compounds targeting downstream signal transduction of single or several endosomal TLRs have been reported. TLR-targeting drugs have been included in clinical trials as vaccine adjuvants or as therapeutic agents for the treatment of diseases, ranging from cancer, infections, asthma and allergy to autoimmune diseases.
Keywords: Nucleic acids, TLR recognition, mechanism of activation, TLR signaling, immunomodulatory compounds, oligodeoxynucleotides, imidazoquinolines
Current Medicinal Chemistry
Title: Recognition of Nucleic Acids by Toll-Like Receptors and Development of Immunomodulatory Drugs
Volume: 17 Issue: 18
Author(s): A. Kuznik, G. Panter and R. Jerala
Affiliation:
Keywords: Nucleic acids, TLR recognition, mechanism of activation, TLR signaling, immunomodulatory compounds, oligodeoxynucleotides, imidazoquinolines
Abstract: Microbial as well as endogenous nucleic acids are recognized by a group of endosomal Toll-like receptors TLR3, TLR7, TLR8 and TLR9. Recent discoveries significantly improved our understanding of molecular mechanism of their activation and their physiological role. Those include recognition of dsRNA through two nucleic acid binding sites of TLR3 ectodomain, activation of TLR9 by phosphodiester backbone of ssDNA, independent of the nucleotide sequence and phosphorothioate modified bonds, and the role of proteolysis in activation of TLR9. In addition, proteins that chaperone nucleic acids, such as HMGB1 or LL-37, have been described to mediate TLR activation. There is growing evidence that supports involvement of endosomal TLRs in a number of autoimmune diseases, suggesting a therapeutic potential of immunomodulatory endosomal TLR ligands. So far, inhibitory nucleic acids against TLR7, TLR8 and TLR9 as well as small compounds targeting downstream signal transduction of single or several endosomal TLRs have been reported. TLR-targeting drugs have been included in clinical trials as vaccine adjuvants or as therapeutic agents for the treatment of diseases, ranging from cancer, infections, asthma and allergy to autoimmune diseases.
Export Options
About this article
Cite this article as:
Kuznik A., Panter G. and Jerala R., Recognition of Nucleic Acids by Toll-Like Receptors and Development of Immunomodulatory Drugs, Current Medicinal Chemistry 2010; 17 (18) . https://dx.doi.org/10.2174/092986710791163957
DOI https://dx.doi.org/10.2174/092986710791163957 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Immunomodulatory and Anti-inflammatory Effects of Thymoquinone
Cardiovascular & Hematological Disorders-Drug Targets Seasonal Allergic Rhinitis
Recent Patents on Inflammation & Allergy Drug Discovery Crystal Engineering to Design of Solids: From Single to Multicomponent Organic Materials
Mini-Reviews in Organic Chemistry Functional Crosstalk Between β2-adrenoreceptor and Muscarinic Acetylcholine Receptor: Implications for Gene-Gene Interactions and Bronchodilatory Responses in Patients with Asthma and COPD
Current Pharmacogenomics and Personalized Medicine The Potential of Ellagic Acid as a Possible Antimalarial Drug Candidate
Current Bioactive Compounds Gender Differences in Metabolic Syndrome – A Key Research Issue
Endocrine, Metabolic & Immune Disorders - Drug Targets Policy and Adolescent Tobacco Use Prevention
Adolescent Psychiatry Pharmacogenomics of COPD
Current Pharmacogenomics p38 MAP Kinase Inhibitors as Anti inflammatory Agents
Mini-Reviews in Medicinal Chemistry Leptin and the Ob-Receptor as Anti-Obesity Target: Recent In Silico Advances in the Comprehension of the Protein-Protein Interaction and Rational Drug Design of Anti- Obesity Lead Compounds
Current Pharmaceutical Design Platelet-Activating Factor (PAF): A Review of its Role in Asthma and Clinical Efficacy of PAF Antagonists in the Disease Therapy
Recent Patents on Inflammation & Allergy Drug Discovery Quality of Life for Children with Allergic Skin Diseases
Current Pediatric Reviews Overview of the Primary Structure, Tissue-Distribution, and Functions of Tachykinins and their Receptors
Current Drug Targets Does Metformin Satisfy as an Option for Host-Directed Therapy in COVID-19?
Anti-Infective Agents Natural Marine Anti-inflammatory Products
Mini-Reviews in Medicinal Chemistry Chemokines in Allergy
Current Drug Targets - Inflammation & Allergy Interleukin-4, Interleukin-13, Signal Transducer and Activator of Transcription Factor 6, and Allergic Asthma
Current Molecular Medicine Dry Powder Formulation of Plasmid DNA and siRNA for Inhalation
Current Pharmaceutical Design Pivotal Role of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 in Inflammatory Pulmonary Diseases
Current Protein & Peptide Science Meet the Guest Editor
Combinatorial Chemistry & High Throughput Screening