Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/19958
Title
Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity
Author(s)
Date issued
2014
Citation
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.
Language
Inglés
Document type
review article
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.
MESH
Calcium | Analgesics, 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 Señal | Animales | Ácido Glutámico | Citocinas | Factor de Necrosis Tumoral alfa | Neuronas | Plasticidad Neuronal | Astrocitos | Humanos | Neurogla | Transmisión Sinóptica | Receptores AMPA | Receptores de GABA-A | Inflamación | Neuralgia | Calcio | Receptores de Glutamato | Analgésicos Opioides | Receptores de N-Metil-D-Aspartato
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