2026-08-05T11:38:43Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/199582024-11-28T20:22:52Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Olmos, Gabriel author Llado, Jeronia author 2014 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. 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. 10.1155/2014/861231 1466-1861 0962-9351 Mediators of Inflammation http://hdl.handle.net/20.500.13003/11404 24966471 L373279697 2-s2.0-84902144244 http://hdl.handle.net/20.500.12105/19958 336614600001 Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity