Abstract
Innate immune responses in the central nervous system must be tightly regulated as unrestrained activation generates a chronic inflammatory environment that can contribute to neurodegeneration and autoimmunity. Microglia express a wide variety of receptors of the innate immune system and are competent responders to danger. Toll-like receptor-, NOD-like receptor- and RIG1-like receptor mediated activation of microglia leads to the production of pro-inflammatory cytokines and to the upregulation of molecules implicated in activation of the adaptive immune system. Activated microglia are a characteristic feature of many neuroinflammatory disorders and they represent an attractive therapeutic target.
This review describes the mechanisms that are at play to restrain microglia activation under homeostatic conditions, such as CD172a, CD200R, SIGIRR and TREM2-mediated signaling, as well as dynamic inhibitory mechanisms that are at play during inflammatory conditions, such as adenosine receptor-mediated signaling. In addition, intracellular activating and inhibitory signaling cascades are summarized in detail and their therapeutic potential is analyzed.
Keywords: Adenosine receptor, microglia, NOD-like receptor, nuclear factor-B, regulation, RIG1-like receptor, Toll-like receptor, innate immunity, pattern-recognition receptors, PRR, PAMPs, DAMPs, leucine-rich repeats, interferon-regulatory factor, MyD88, TRAM, SARM, Alzheimer's disease, NACHT domain, caspase recruitment domain, MHCII, Listeria monocytogenes, Staphylococcus aureus, N. meningitidis, B. burgdorferi, S. pneumoniae, XIAP, flaviviruses, vesicular stomatitis virus, West Nile virus, coronavirus, mouse hepatitis virus, SIGIRR, ITIM, DC-SIGN, ADORA, TRIAD3A, TRAIL, RIP1, IFN therapy, deubiquitinating enzyme, NEMO, SIKE, Glucocorticoid receptor, ICEBERG, CD172a, CD200R, TREM2
CNS & Neurological Disorders - Drug Targets
Title: Regulation of Innate Immune Responses in the Central Nervous System
Volume: 10 Issue: 1
Author(s): Jeffrey J. Bajramovic
Affiliation:
Keywords: Adenosine receptor, microglia, NOD-like receptor, nuclear factor-B, regulation, RIG1-like receptor, Toll-like receptor, innate immunity, pattern-recognition receptors, PRR, PAMPs, DAMPs, leucine-rich repeats, interferon-regulatory factor, MyD88, TRAM, SARM, Alzheimer's disease, NACHT domain, caspase recruitment domain, MHCII, Listeria monocytogenes, Staphylococcus aureus, N. meningitidis, B. burgdorferi, S. pneumoniae, XIAP, flaviviruses, vesicular stomatitis virus, West Nile virus, coronavirus, mouse hepatitis virus, SIGIRR, ITIM, DC-SIGN, ADORA, TRIAD3A, TRAIL, RIP1, IFN therapy, deubiquitinating enzyme, NEMO, SIKE, Glucocorticoid receptor, ICEBERG, CD172a, CD200R, TREM2
Abstract: Innate immune responses in the central nervous system must be tightly regulated as unrestrained activation generates a chronic inflammatory environment that can contribute to neurodegeneration and autoimmunity. Microglia express a wide variety of receptors of the innate immune system and are competent responders to danger. Toll-like receptor-, NOD-like receptor- and RIG1-like receptor mediated activation of microglia leads to the production of pro-inflammatory cytokines and to the upregulation of molecules implicated in activation of the adaptive immune system. Activated microglia are a characteristic feature of many neuroinflammatory disorders and they represent an attractive therapeutic target.
This review describes the mechanisms that are at play to restrain microglia activation under homeostatic conditions, such as CD172a, CD200R, SIGIRR and TREM2-mediated signaling, as well as dynamic inhibitory mechanisms that are at play during inflammatory conditions, such as adenosine receptor-mediated signaling. In addition, intracellular activating and inhibitory signaling cascades are summarized in detail and their therapeutic potential is analyzed.
Export Options
About this article
Cite this article as:
J. Bajramovic Jeffrey, Regulation of Innate Immune Responses in the Central Nervous System, CNS & Neurological Disorders - Drug Targets 2011; 10 (1) . https://dx.doi.org/10.2174/187152711794488610
DOI https://dx.doi.org/10.2174/187152711794488610 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...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
-
Tapasin and Human Leukocyte Antigen Class I Dysregulation Correlates with Survival in Glioblastoma Multiforme
Anti-Cancer Agents in Medicinal Chemistry Amino Acid Transporter-Targeted Radiotracers for Molecular Imaging in Oncology
Current Medicinal Chemistry Design of New Improved Curcumin Derivatives to Multi-targets of Cancer and Inflammation
Current Drug Targets Potential Pathways for CNS Drug Delivery Across the Blood-Cerebrospinal Fluid Barrier
Current Pharmaceutical Design Hypoxia in Du-145 Prostate Cancer Xenografts After Estramustine Phosphate and Radiotherapy
Current Radiopharmaceuticals Potential Therapeutic Application of Chondroitin Sulfate/Dermatan Sulfate
Current Drug Discovery Technologies Is the Epithelial-to-Mesenchymal Transition Clinically Relevant for the Cancer Patient?
Current Pharmaceutical Biotechnology Telomere Maintenance as Therapeutic Target in Embryonal Tumours
Anti-Cancer Agents in Medicinal Chemistry The Effect of Chemotherapy/Radiotherapy on Cancerous Pattern Recognition by NK Cells
Current Medicinal Chemistry The Relationship Between Epilepsy and Depression: An Update
Current Medicinal Chemistry Computer Aided Drug Design Approaches for Identification of Novel Autotaxin (ATX) Inhibitors
Current Medicinal Chemistry Cancer Stem Cells in Prostate Cancer Chemoresistance
Current Cancer Drug Targets Lipid-Based Drug Delivery Systems for Cancer Treatment
Current Drug Targets Regulation of Cell Death and Survival by Resveratrol: Implications for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Smart Synthetic Polymer Nanocarriers for Controlled and Site-Specific Drug Delivery
Current Topics in Medicinal Chemistry Safety of Multi-Targeted Kinase Inhibitors as Monotherapy Treatment of Cancer: A Systematic Review of the Literature
Current Drug Safety Arachidonic Acid Induces the Migration of MDA-MB-231 Cells by Activating Raft-associated Leukotriene B4 Receptors
Clinical Cancer Drugs Small Regulatory Molecules Acting Big in Cancer: Potential Role of Mito-miRs in Cancer
Current Molecular Medicine Actions of Melatonin, Its Structural and Functional Analogs in the Central Nervous System and the Significance of Metabolism
Central Nervous System Agents in Medicinal Chemistry The Place of Somatostatin Analogs in the Diagnosis and Treatment of the Neuoroendocrine Glands Tumors
Recent Patents on Anti-Cancer Drug Discovery