Identifier to cite or link to this item: http://hdl.handle.net/20.500.13003/11404
Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity
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DOI: 10.1155/2014/861231
ISSN: 0962-9351
eISSN: 1466-1861
WOS ID: 000336614600001
Scopus EID: 2-s2.0-84902144244
PMID: 24966471
Embase PUI: L373279697
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2014Document type
review articleCitation
Olmos Bonafe G, Llado Vich J. Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity. Mediat Inflamm. 2014;2014:861231. Epub 2014 May 21.Abstract
Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that exerts both homeostatic and pathophysiological roles in the central nervous system. In pathological conditions, microglia release large amounts of TNF-alpha; this de novo production of TNF-alpha is an important component of the so-called neuroinflammatory response that is associated with several neurological disorders. In addition, TNF-alpha can potentiate glutamate-mediated cytotoxicity by two complementary mechanisms: indirectly, by inhibiting glutamate transport on astrocytes, and directly, by rapidly triggering the surface expression of Ca+ 2 permeable-AMPA receptors and NMDA receptors, while decreasing inhibitory GABA(A) receptors on neurons. Thus, the net effect of TNF-alpha is to alter the balance of excitation and inhibition resulting in a higher synaptic excitatory/inhibitory ratio. This review summarizes the current knowledge of the cellular and molecular mechanisms by which TNF-alpha links the neuroinflammatory and excitotoxic processes that occur in several neurodegenerative diseases, but with a special emphasis on amyotrophic lateral sclerosis (ALS). As microglial activation and upregulation of TNF-alpha expression is a common feature of several CNS diseases, as well as chronic opioid exposure and neuropathic pain, modulating TNF-alpha signaling may represent a valuable target for intervention.
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https://dx.doi.org/10.1155/2014/861231MeSH
CalciumAnalgesics, Opioid
Receptors, Glutamate
Receptors, N-Methyl-D-Aspartate
Astrocytes
Receptors, AMPA
Humans
Inflammation
Neuralgia
Neuroglia
Synaptic Transmission
Neurons
Receptors, GABA-A
Cytokines
Neuronal Plasticity
Tumor Necrosis Factor-alpha
Animals
Signal Transduction
Glutamic Acid
DeCS
Transducción de SeñalAnimales
Ácido Glutámico
Citocinas
Factor de Necrosis Tumoral alfa
Neuronas
Plasticidad Neuronal
Astrocitos
Humanos
Neuroglía
Transmisión Sináptica
Receptores AMPA
Receptores de GABA-A
Inflamación
Neuralgia
Calcio
Receptores de Glutamato
Analgésicos Opioides
Receptores de N-Metil-D-Aspartato