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• W2052330193 endingPage "38" @default.
• W2052330193 startingPage "32" @default.
• W2052330193 abstract "In acute ischaemic brain injury and chronic neurodegeneration, the primary step leading to excitotoxicity and cell death is the excessive and/or prolonged activation of glutamate (Glu) receptors, followed by intracellular calcium (Ca(2+)) overload. These steps lead to several effects: a persistent depolarisation of neurons, mitochondrial dysfunction resulting in energy failure, an increased production of reactive oxygen species (ROS), an increase in the concentration of cytosolic Ca(2+) [Ca(2+)]i, increased mitochondrial Ca(2+) uptake, and the activation of self-destructing enzymatic mechanisms. Antagonists for NMDA receptors (NMDARs) are expected to display neuroprotective effects, but no evidence to support this hypothesis has yet been reported. A number of clinical trials using NMDAR antagonists have failed to demonstrate neuroprotective effects, either by reducing brain injury or by preventing neurodegeneration. Recent advances in NMDAR research have provided an explanation for this phenomenon. Synaptic and extrasynaptic NMDARs are composed of different subunits (GluN2A and GluN2B) that demonstrate opposing effects. Synaptic GluN2A-containing and extrasynaptic GluN2B-containing NMDARs have different co-agonists: d-serine for synaptic NMDARs and glycine for extrasynaptic NMDARs. Both co-agonists are of glial origin. The mechanisms of cell destruction or cell survival in response to the activation of NMDAR receptors depend in part on [Ca(2+)]i and the route of entry of this ion and more significantly on the subunit composition and localisation of the NMDARs. While synaptic NMDAR activation is involved in neuroprotection, the stimulation of extrasynaptic NMDARs, which are composed of GluN2B subunits, triggers cell destruction pathways and may play a key role in the neurodegeneration associated with Glu-induced excitotoxicity. In addition, it has been found that synaptic and extrasynaptic NMDA receptors have opposing effects in determining the fate of neurons. This result has led to the targeting of nonsynaptic GluN2B-containing NMDARs as promising candidates for drug research. Under hypoxic conditions, it is likely that the failure of synaptic glutamatergic transmission, the impairment of the GluN2A-activated neuroprotective cascade, and the persistent over-activation of extrasynaptic GluN2B-containing NMDARs lead to excitotoxicity. Fluoxetine, a drug widely used in clinical practice as an antidepressant, has been found to selectively block GluNR2B-containing NMDARs. Therefore, it seems to be a potential candidate for neuroprotection." @default.
• W2052330193 created "2016-06-24" @default.
• W2052330193 creator A5014941638 @default.
• W2052330193 creator A5038985063 @default.
• W2052330193 creator A5070442560 @default.
• W2052330193 date "2013-04-01" @default.
• W2052330193 modified "2023-10-18" @default.
• W2052330193 title "Role of nonsynaptic GluN2B-containing NMDA receptors in excitotoxicity: Evidence that fluoxetine selectively inhibits these receptors and may have neuroprotective effects" @default.
• W2052330193 cites W1503516869 @default.
• W2052330193 cites W1533853049 @default.
• W2052330193 cites W1551854265 @default.
• W2052330193 cites W1876061808 @default.
• W2052330193 cites W1884366104 @default.
• W2052330193 cites W1964151230 @default.
• W2052330193 cites W1965202553 @default.
• W2052330193 cites W1970103114 @default.
• W2052330193 cites W1970752307 @default.
• W2052330193 cites W1973436856 @default.
• W2052330193 cites W1977529472 @default.
• W2052330193 cites W1980059018 @default.
• W2052330193 cites W1981238903 @default.
• W2052330193 cites W1985448600 @default.
• W2052330193 cites W1986790448 @default.
• W2052330193 cites W1986913584 @default.
• W2052330193 cites W1989034945 @default.
• W2052330193 cites W1993536619 @default.
• W2052330193 cites W1993636230 @default.
• W2052330193 cites W1993716787 @default.
• W2052330193 cites W1994814395 @default.
• W2052330193 cites W1995334423 @default.
• W2052330193 cites W1997962003 @default.
• W2052330193 cites W2002831316 @default.
• W2052330193 cites W2006815009 @default.
• W2052330193 cites W2007001870 @default.
• W2052330193 cites W2007683107 @default.
• W2052330193 cites W2020525904 @default.
• W2052330193 cites W2021700369 @default.
• W2052330193 cites W2022805748 @default.
• W2052330193 cites W2023283315 @default.
• W2052330193 cites W2027900655 @default.
• W2052330193 cites W2028594041 @default.
• W2052330193 cites W2029064264 @default.
• W2052330193 cites W2031326543 @default.
• W2052330193 cites W2035750459 @default.
• W2052330193 cites W2036796078 @default.
• W2052330193 cites W2037210922 @default.
• W2052330193 cites W2038955102 @default.
• W2052330193 cites W2040806880 @default.
• W2052330193 cites W2040936201 @default.
• W2052330193 cites W2041412776 @default.
• W2052330193 cites W2043885768 @default.
• W2052330193 cites W2045197372 @default.
• W2052330193 cites W2046801007 @default.
• W2052330193 cites W2047894110 @default.
• W2052330193 cites W2048557710 @default.
• W2052330193 cites W2051423370 @default.
• W2052330193 cites W2052822734 @default.
• W2052330193 cites W2057925384 @default.
• W2052330193 cites W2059040821 @default.
• W2052330193 cites W2064244595 @default.
• W2052330193 cites W2064261539 @default.
• W2052330193 cites W2065043991 @default.
• W2052330193 cites W2065887140 @default.
• W2052330193 cites W2070277010 @default.
• W2052330193 cites W2070822582 @default.
• W2052330193 cites W2071940267 @default.
• W2052330193 cites W2073221051 @default.
• W2052330193 cites W2074125037 @default.
• W2052330193 cites W2074792377 @default.
• W2052330193 cites W2078932584 @default.
• W2052330193 cites W2081070804 @default.
• W2052330193 cites W2082618148 @default.
• W2052330193 cites W2082738188 @default.
• W2052330193 cites W2086215197 @default.
• W2052330193 cites W2086766432 @default.
• W2052330193 cites W2089841912 @default.
• W2052330193 cites W2091849927 @default.
• W2052330193 cites W2093716487 @default.
• W2052330193 cites W2095159395 @default.
• W2052330193 cites W2097095684 @default.
• W2052330193 cites W2097136804 @default.
• W2052330193 cites W2098815266 @default.
• W2052330193 cites W2102789443 @default.
• W2052330193 cites W2104417933 @default.
• W2052330193 cites W2108025392 @default.
• W2052330193 cites W2109334096 @default.
• W2052330193 cites W2109909801 @default.
• W2052330193 cites W2112923399 @default.
• W2052330193 cites W2113179767 @default.
• W2052330193 cites W2114163624 @default.
• W2052330193 cites W2115296629 @default.
• W2052330193 cites W2118925874 @default.
• W2052330193 cites W2124134368 @default.
• W2052330193 cites W2129267808 @default.
• W2052330193 cites W2130311440 @default.
• W2052330193 cites W2135781323 @default.
• W2052330193 cites W2140047003 @default.
• W2052330193 cites W2151675314 @default.

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