Abstract
In this review we discuss that peripheral and central activation of the Toll-like receptor 2/4 (TLR2/4) Radical Cycle may underpin the pathophysiology of immune-related chronic fatigue secondary to other medical diseases and conditions. The TLR Radical Cycle plays a role in illnesses and conditions that are disproportionately commonly comorbid with secondary chronic fatigue, including a) neuroinflammatory disorders, e.g. Parkinson’s disease, stroke, depression, psychological stressors, and b) systemic disorders, e.g. (auto)immune disorders, chronic obstructive pulmonary disease, ankylosing spondylitis, chronic kidney disease, inflammatory bowel disease, cardiovascular disease, incl. myocardial infarction, cancer and its treatments. Increased TLR signaling is driven by activated immuneinflammatory and oxidative and nitrosative stress pathways, pathogen derived molecular patterns, including lipopolysaccharides, and damage associated molecular patterns (DAMPs). Newly formed redox-derived DAMPs, secondary to oxidative processes, may further activate the TLR complex leading to an auto-amplifying TLR Radical feedback loop. Increased gut permeability with translocation of gram negative bacteria and LPS, which activates the TLR Radical Cycle, is another pathway that may play a role in most of the abovementioned diseases and the secondary fatigue accompanying them. It is concluded that secondary fatigue may be associated with activation of the TLR Radical Cycle pathway due to activated immune-inflammatory pathways, classical and redox-derived DAMPs and PAMPs plays a role in its pathophysiology. Such an activation of the TLR Radical Cycle pathway may also explain why the abovementioned conditions are primed for an increased expression of secondary chronic fatigue. Targeting the TLR Radical Cycle pathway may be an effective method to treat TLR-Radical Cycle-related diseases such as secondary chronic fatigue.
Keywords: Antioxidants, chronic fatigue syndrome, depression, inflammation, myalgic encephalomyelitis, oxidative and nitrosative stress, lipopolysaccharides, toll-like receptor.
CNS & Neurological Disorders - Drug Targets
Title:The Toll-Like Receptor Radical Cycle Pathway: A New Drug Target in Immune-Related Chronic Fatigue
Volume: 14 Issue: 7
Author(s): Kurt Lucas, Gerwyn Morris, George Anderson and Michael Maes
Affiliation:
Keywords: Antioxidants, chronic fatigue syndrome, depression, inflammation, myalgic encephalomyelitis, oxidative and nitrosative stress, lipopolysaccharides, toll-like receptor.
Abstract: In this review we discuss that peripheral and central activation of the Toll-like receptor 2/4 (TLR2/4) Radical Cycle may underpin the pathophysiology of immune-related chronic fatigue secondary to other medical diseases and conditions. The TLR Radical Cycle plays a role in illnesses and conditions that are disproportionately commonly comorbid with secondary chronic fatigue, including a) neuroinflammatory disorders, e.g. Parkinson’s disease, stroke, depression, psychological stressors, and b) systemic disorders, e.g. (auto)immune disorders, chronic obstructive pulmonary disease, ankylosing spondylitis, chronic kidney disease, inflammatory bowel disease, cardiovascular disease, incl. myocardial infarction, cancer and its treatments. Increased TLR signaling is driven by activated immuneinflammatory and oxidative and nitrosative stress pathways, pathogen derived molecular patterns, including lipopolysaccharides, and damage associated molecular patterns (DAMPs). Newly formed redox-derived DAMPs, secondary to oxidative processes, may further activate the TLR complex leading to an auto-amplifying TLR Radical feedback loop. Increased gut permeability with translocation of gram negative bacteria and LPS, which activates the TLR Radical Cycle, is another pathway that may play a role in most of the abovementioned diseases and the secondary fatigue accompanying them. It is concluded that secondary fatigue may be associated with activation of the TLR Radical Cycle pathway due to activated immune-inflammatory pathways, classical and redox-derived DAMPs and PAMPs plays a role in its pathophysiology. Such an activation of the TLR Radical Cycle pathway may also explain why the abovementioned conditions are primed for an increased expression of secondary chronic fatigue. Targeting the TLR Radical Cycle pathway may be an effective method to treat TLR-Radical Cycle-related diseases such as secondary chronic fatigue.
Export Options
About this article
Cite this article as:
Lucas Kurt, Morris Gerwyn, Anderson George and Maes Michael, The Toll-Like Receptor Radical Cycle Pathway: A New Drug Target in Immune-Related Chronic Fatigue, CNS & Neurological Disorders - Drug Targets 2015; 14 (7) . https://dx.doi.org/10.2174/1871527314666150317224645
DOI https://dx.doi.org/10.2174/1871527314666150317224645 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Heart and Brain Axis Targets in CNS Neurological Disorders
Recently there has been a surge of interest in delving deeper into the complex interplay between the heart and brain. This fascination stems from a growing recognition of the profound influence each organ holds over the other, particularly in the realm of central nervous system (CNS) neurological disorders. The purpose ...read more
Lifestyle Interventions to Prevent and Treat Cognitive Impairment and Dementia
More than 55 million people live with dementia worldwide. By 2050, the population affected by dementia will exceed 139 million individuals. Mild cognitive impairment (MCI) is a pre-dementia stage, also known as prodromal dementia, affecting older adults. MCI emerges years before the manifestation of dementia but can be avoidable and ...read more
Pathogenic Proteins in Neurodegenerative Diseases: From Mechanisms to Treatment Modalities
The primary objective of this thematic issue is to elucidate the molecular mechanisms by which pathogenic proteins contribute to neurodegenerative diseases and to highlight current and emerging therapeutic strategies aimed at mitigating their effects. By bringing together cutting-edge research and reviews, this issue aims to: 1.Enhance Understanding: Provide a comprehensive ...read more
Role of glial cells in autism spectrum disorder: Molecular mechanism and therapeutic approaches
Emerging evidence suggests that glial cells may play a pivotal role in neuroanatomical and behavioral changes found in autism spectrum disorder (ASD). Many individuals with ASD experience a neuro-immune system abnormalities throughout life, which implicates a potential role of microglia in the pathogenesis of ASD. Dysfunctional astrocytes and oligodendrocytes were ...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
-
Anemia in Chronic Heart Failure - Clinical and Prognostic Significance
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Stem Cell and Gene Therapeutic Strategies for the Treatment of Multiple Sclerosis
Current Molecular Medicine Therapeutic Applications of Mesenchymal Stem Cells: A Comprehensive Review
Current Stem Cell Research & Therapy Treatment of Chronic Peripheral Arterial Disease
Current Vascular Pharmacology Saturation of the Human Phenome
Current Genomics Correlation of Urine Biomarkers: Microalbuminuria and Spot Urine Protein among Diabetic Patients. Application of Spot Urine Protein in Diabetic Kidney Disease, Nephropathy, Proteinuria Estimation, Diagnosing and Monitoring
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) Therapy Against Reperfusion-induced Microvascular Injury
Current Pharmaceutical Design Preconditioning of the Myocardium by Volatile Anesthetics
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Influence of Chronic Kidney Disease Development and Renin-angiotensin System Inhibition on Cardiovascular Prognosis
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Selective Serotonin Re-Uptake Inhibitors and Hyponatremia in Acutely Medically-Ill Inpatients
Current Drug Safety Left Ventricular Non-compaction: From Recognition to Treatment
Current Pharmaceutical Design Life-Threatening Respiratory Syncytial Virus Disease in Children
Current Respiratory Medicine Reviews Cardiac Stem Cell Regeneration in Metabolic Syndrome
Current Pharmaceutical Design Editorial [ Hot Topic:The Medicinal Chemistry of New Agents to Treat Diabetes and Obesity (Guest Editor: Jie-Fei Cheng)]
Current Topics in Medicinal Chemistry Ghrelin in Obesity, Physiological and Pharmacological Considerations
Mini-Reviews in Medicinal Chemistry Nitric Oxide and Dietary Factors: Part I Nitric Oxide Synthesis and Action
Vascular Disease Prevention (Discontinued) Renal Nerve Ablation for Hypertensive Patients with Chronic Kidney Disease
Current Vascular Pharmacology East Meets West in the Search for Alzheimers Therapeutics - Novel Dimeric Inhibitors from Tacrine and Huperzine A
Current Alzheimer Research Optical Techniques in the Assessment of Peripheral Arterial Disease
Current Vascular Pharmacology Pharmacokinetic Interactions Between Herbal Medicines and Prescribed Drugs: Focus on Drug Metabolic Enzymes and Transporters
Current Drug Metabolism