Abstract
Inflammatory signals generated within the brain and peripheral nervous system direct diverse biological processes. Key amongst the inflammatory molecules is tumor necrosis factor-alpha (TNF-α), a potent pro-inflammatory cytokine that, via binding to its associated receptors, is considered to be a master regulator of cellular cascades that control a number of diverse processes coupled to cell viability, gene expression, synaptic integrity and ion homeostasis. Whereas a self-limiting neuroinflammatory response generally results in the resolution of an intrinsically or extrinsically triggered insult by the elimination of toxic material or injured tissue to restore brain homeostasis and function, in the event of an unregulated reaction, where the immune response persists, inappropriate chronic neuroinflammation can ensue. Uncontrolled neuroinflammatory activity can induce cellular dysfunction and demise, and lead to a selfpropagating cascade of harmful pathogenic events. Such chronic neuroinflammation is a typical feature across a range of debilitating common neurodegenerative diseases, epitomized by Alzheimers disease, Parkinsons disease and amyotrophic lateral sclerosis, in which TNF-α expression appears to be upregulated and may represent a valuable target for intervention. Elaboration of the protective homeostasis signaling cascades from the harmful pathogenic ones that likely drive disease onset and progression could aid in the clinical translation of approaches to lower brain and peripheral nervous system TNF-α levels, and amelioration of inappropriate neuroinflammation.
Keywords: Tumor necrosis factor-alpha, neuroinflammation, cytokine, chemokine, neurodegeneration, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Japanese encephalitis, dementia, Thalidomide, Revlimid
CNS & Neurological Disorders - Drug Targets
Title: Targeting TNF-Alpha to Elucidate and Ameliorate Neuroinflammation in Neurodegenerative Diseases
Volume: 10 Issue: 3
Author(s): Kathryn A. Frankola, Nigel H. Greig, Weiming Luo and David Tweedie
Affiliation:
Keywords: Tumor necrosis factor-alpha, neuroinflammation, cytokine, chemokine, neurodegeneration, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Japanese encephalitis, dementia, Thalidomide, Revlimid
Abstract: Inflammatory signals generated within the brain and peripheral nervous system direct diverse biological processes. Key amongst the inflammatory molecules is tumor necrosis factor-alpha (TNF-α), a potent pro-inflammatory cytokine that, via binding to its associated receptors, is considered to be a master regulator of cellular cascades that control a number of diverse processes coupled to cell viability, gene expression, synaptic integrity and ion homeostasis. Whereas a self-limiting neuroinflammatory response generally results in the resolution of an intrinsically or extrinsically triggered insult by the elimination of toxic material or injured tissue to restore brain homeostasis and function, in the event of an unregulated reaction, where the immune response persists, inappropriate chronic neuroinflammation can ensue. Uncontrolled neuroinflammatory activity can induce cellular dysfunction and demise, and lead to a selfpropagating cascade of harmful pathogenic events. Such chronic neuroinflammation is a typical feature across a range of debilitating common neurodegenerative diseases, epitomized by Alzheimers disease, Parkinsons disease and amyotrophic lateral sclerosis, in which TNF-α expression appears to be upregulated and may represent a valuable target for intervention. Elaboration of the protective homeostasis signaling cascades from the harmful pathogenic ones that likely drive disease onset and progression could aid in the clinical translation of approaches to lower brain and peripheral nervous system TNF-α levels, and amelioration of inappropriate neuroinflammation.
Export Options
About this article
Cite this article as:
A. Frankola Kathryn, H. Greig Nigel, Luo Weiming and Tweedie David, Targeting TNF-Alpha to Elucidate and Ameliorate Neuroinflammation in Neurodegenerative Diseases, CNS & Neurological Disorders - Drug Targets 2011; 10 (3) . https://dx.doi.org/10.2174/187152711794653751
DOI https://dx.doi.org/10.2174/187152711794653751 |
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
-
Protective Ability of Perovskia abrotanoides Karel Root Extract on the Aggregation of Protein In Vitro
The Natural Products Journal Calpain Inhibition: A Therapeutic Strategy Targeting Multiple Disease States
Current Pharmaceutical Design Synthetic Methods for the Preparation of Triazepandiones and Review of their Applications
Current Organic Chemistry The Identification and Characterization of Excitotoxic Nerve-endings in Alzheimer Disease
Current Alzheimer Research Molecular, Cellular and Clinical Aspects of Intracerebral Hemorrhage: Are the Enemies Within?
Current Neuropharmacology Induced Adaptive Resistance to Nitrooxidative Stress in the CNS: Therapeutic Implications
Central Nervous System Agents in Medicinal Chemistry Structural Activity Relationship and Importance of Benzothiazole Derivatives in Medicinal Chemistry: A Comprehensive Review
Mini-Reviews in Organic Chemistry Editorial [Hot Topic: Advances in Alzheimer Therapy: Development of Innovative New Strategies (Guest Editors: Nigel H. Greig, Ezio Giacobini and Debomoy K. Lahiri)]
Current Alzheimer Research In vitro Generated Mesenchymal Stem Cells: Suitable Tools to Target Insulin Dependent Diabetes Mellitus?
Current Stem Cell Research & Therapy The Development and Progression of Atherosclerosis: Evidence supporting a Role for Endoplasmic Reticulum (ER) Stress Signaling
Cardiovascular & Hematological Disorders-Drug Targets Recent Advances in Nanoneurology for Drug Delivery to the Brain
Current Nanoscience Glutamate-Mediated Signaling and Autism Spectrum Disorders: Emerging Treatment Targets
Current Pharmaceutical Design The Molecular Pathology of Huntingtons Disease (HD)
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Plant-Derived Natural Compounds for the Treatment of Amyotrophic Lateral Sclerosis: An Update
Current Neuropharmacology Decreased Regenerative Capacity of Oligodendrocyte Progenitor Cells (NG2-Glia) in the Ageing Brain: A Vicious Cycle of Synaptic Dysfunction, Myelin Loss and Neuronal Disruption?
Current Alzheimer Research Structure – Function Relationships of Pre-Fibrillar Protein Assemblies in Alzheimers Disease and Related Disorders
Current Alzheimer Research Cell and Gene Therapies for Refractory Epilepsy
Current Neuropharmacology Recent Patents Review on Intranasal Administration for CNS Drug Delivery
Recent Patents on Drug Delivery & Formulation Screening of Natural Compounds Against SOD1 as a Therapeutic Target for Amyotrophic Lateral Sclerosis
Letters in Drug Design & Discovery Reacting to Stress: Radical Cellular Pathways for Novel Drug Development
Current Neurovascular Research