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.
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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 |
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