Abstract
The identification of the TLRs as key sensors of microbial infection has presented a series of new targets for drug development. The TLRs are linked to the most powerful inflammatory pathways in mammals. The question arises from the start: do we wish to stimulate TLR signaling in order to eradicate specific infections and/or neoplastic diseases? Or do we wish to block TLR signaling to treat inflammatory diseases? If we accept that it would be useful to modulate TLR signaling, the next step is to identify the correct molecular target(s) for the task. Perhaps it might even be possible to exercise selectivity, modulating some aspects of TLR signaling and not others. Classical and reverse genetic analyses offer insight into the possibilities that exist, and point to specific checkpoints within signaling pathways at which modulation might normally be imposed.
Keywords: TNF neutralization, sterile inflammation, microbial adjuvants, MyD88-dependent signal transduction, Trif mutation
Current Pharmaceutical Design
Title: TLR Signaling Pathways: Opportunities for Activation and Blockade in Pursuit of Therapy
Volume: 12 Issue: 32
Author(s): K. Hoebe, Z. Jiang, P. Georgel, K. Tabeta, E. Janssen, X. Du and B. Beutler
Affiliation:
Keywords: TNF neutralization, sterile inflammation, microbial adjuvants, MyD88-dependent signal transduction, Trif mutation
Abstract: The identification of the TLRs as key sensors of microbial infection has presented a series of new targets for drug development. The TLRs are linked to the most powerful inflammatory pathways in mammals. The question arises from the start: do we wish to stimulate TLR signaling in order to eradicate specific infections and/or neoplastic diseases? Or do we wish to block TLR signaling to treat inflammatory diseases? If we accept that it would be useful to modulate TLR signaling, the next step is to identify the correct molecular target(s) for the task. Perhaps it might even be possible to exercise selectivity, modulating some aspects of TLR signaling and not others. Classical and reverse genetic analyses offer insight into the possibilities that exist, and point to specific checkpoints within signaling pathways at which modulation might normally be imposed.
Export Options
About this article
Cite this article as:
Hoebe K., Jiang Z., Georgel P., Tabeta K., Janssen E., Du X. and Beutler B., TLR Signaling Pathways: Opportunities for Activation and Blockade in Pursuit of Therapy, Current Pharmaceutical Design 2006; 12 (32) . https://dx.doi.org/10.2174/138161206778743466
DOI https://dx.doi.org/10.2174/138161206778743466 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Nitric Oxide-Derived Oxidants with a Focus on Peroxynitrite: Molecular Targets,Cellular Responses and Therapeutic Implications
Current Pharmaceutical Design Traumatic Brain Injury and Blood-Brain Barrier Cross-Talk
CNS & Neurological Disorders - Drug Targets The Role of Minocycline in Ischemia-Reperfusion Injury: A Comprehensive Review of an Old Drug with New Implications
Recent Patents on Cardiovascular Drug Discovery The Role of Matrix Metalloproteinases in Diabetes Mellitus
Current Topics in Medicinal Chemistry Pharmacotherapy of Aortic Stenosis-Success or Failure?
Current Pharmaceutical Biotechnology Safety and Efficacy of Teplizumab for Treatment of Type One Diabetes Mellitus: A Systematic Review and Meta-Analysis
Endocrine, Metabolic & Immune Disorders - Drug Targets Design, Characterization and Pre-Clinical Evaluation of Aceclofenac Loaded Algino-gelatin Microspheres for Targeted Drug Delivery
Drug Delivery Letters Pluronic-Based Core/Shell Nanoparticles for Drug Delivery and Diagnosis
Current Medicinal Chemistry Role of the Endosomal ESCRT Machinery in HIV-1 Vpu-Induced Down- Regulation of BST2/Tetherin
Current HIV Research Role of Chymase in Preeclampsia
Current Vascular Pharmacology Common Molecular Targets for Bioactive Food Components and Drugs
Current Pediatric Reviews Hereditary Heterozygous C2 Deficiency: Variable Clinical and Serological Manifestations Among Three Sisters
Current Rheumatology Reviews The Relationship Between Diabetes Mellitus, Geriatric Syndromes, Physical Function, and Gait: A Review of the Literature
Current Diabetes Reviews Impact of Cerebral Malaria on Brain Distribution of Mefloquine
Drug Metabolism Letters Biomarkers in Unstable Carotid Plaque: Physiopathology and Prediction
Cardiovascular & Hematological Agents in Medicinal Chemistry Pathophysiology and Treatment of Fibromyalgia Syndrome
Current Rheumatology Reviews Cytokine Gene Polymorphism in Heart Transplantation: A Review
Current Genomics Prospects for A Schistosome Vaccine
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Bacterial Protein Toxins: Current and Potential Clinical Use
Current Medicinal Chemistry Gene Therapy for Arthritis
Current Drug Targets