Olmos, GabrielLlado, Jeronia2024-07-032024-07-032014Olmos Bonafe G, Llado Vich J. Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity. Mediat Inflamm. 2014;2014:861231. Epub 2014 May 21.0962-9351http://hdl.handle.net/20.500.13003/11404http://hdl.handle.net/20.500.12105/19958Tumor 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.enghttps://creativecommons.org/licenses/by/3.0/CalciumAnalgesics, OpioidReceptors, GlutamateReceptors, N-Methyl-D-AspartateAstrocytesReceptors, AMPAHumansInflammationNeuralgiaNeurogliaSynaptic TransmissionNeuronsReceptors, GABA-ACytokinesNeuronal PlasticityTumor Necrosis Factor-alphaAnimalsSignal TransductionGlutamic Acidreview articleAttribution 3.0 Unported24966471201486123110.1155/2014/8612311466-1861Mediators of Inflammationopen accessTransducción de SeñalAnimalesÁcido GlutámicoCitocinasFactor de Necrosis Tumoral alfaNeuronasPlasticidad NeuronalAstrocitosHumanosNeuroglaTransmisión SinópticaReceptores AMPAReceptores de GABA-AInflamaciónNeuralgiaCalcioReceptores de GlutamatoAnalgésicos OpioidesReceptores de N-Metil-D-Aspartato2-s2.0-84902144244336614600001L373279697