title: Tumor necrosis factor alpha: a link between neuroinflammation and excitotoxicity.
abstract: Tumor necrosis factor alpha (TNF- α) 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-α; this de novo production of TNF-α is an important component of the so-called neuroinflammatory response that is associated with several neurological disorders. In addition, TNF-α 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 GABAA receptors on neurons. Thus, the net effect of TNF-α 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-α 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-α expression is a common feature of several CNS diseases, as well as chronic opioid exposure and neuropathic pain, modulating TNF-α signaling may represent a valuable target for intervention.
authors: Grup de Neurobiologia Cel · lular, Departament de Biologia and Institut Universitari d'Investigacions en Ciències de la Salut, IUNICS, Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain.
authors: Gabriel
authors: G
authors: Olmos
authors: Grup de Neurobiologia Cel · lular, Departament de Biologia and Institut Universitari d'Investigacions en Ciències de la Salut, IUNICS, Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain.
authors: Jerònia
authors: J
authors: Lladó
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D009437:Neuralgia; D009457:Neuroglia / Q000166:cytology; D009473:Neuronal Plasticity; D009474:Neurons / Q000473:pathology*; D018091:Receptors, AMPA / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction; D009435:Synaptic Transmission; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D016207:Cytokines; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid; D002118:Calcium