Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity
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...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/861231 |
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| author | Gabriel Olmos Jerònia Lladó |
| author_facet | Gabriel Olmos Jerònia Lladó |
| author_sort | Gabriel Olmos |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e6bfd0bc6c7440d2b812fbf95b484254 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-e6bfd0bc6c7440d2b812fbf95b4842542025-02-03T01:27:37ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/861231861231Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and ExcitotoxicityGabriel Olmos0Jerònia Lladó1Grup 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, SpainGrup 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, SpainTumor 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.http://dx.doi.org/10.1155/2014/861231 |
| spellingShingle | Gabriel Olmos Jerònia Lladó Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity Mediators of Inflammation |
| title | Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity |
| title_full | Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity |
| title_fullStr | Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity |
| title_full_unstemmed | Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity |
| title_short | Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity |
| title_sort | tumor necrosis factor alpha a link between neuroinflammation and excitotoxicity |
| url | http://dx.doi.org/10.1155/2014/861231 |
| work_keys_str_mv | AT gabrielolmos tumornecrosisfactoralphaalinkbetweenneuroinflammationandexcitotoxicity AT jeroniallado tumornecrosisfactoralphaalinkbetweenneuroinflammationandexcitotoxicity |