)| PMID |
17574754 ( ) |
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| Title | Divergent effects of prostaglandin receptor signaling on neuronal survival. |
| Abstract | Induction of cyclooxygenase-2 (COX-2) with production of prostaglandins occurs in a wide spectrum of acute and chronic neurodegenerative diseases and is associated with neuronal death. Inhibition of the COX-2 pathway and downstream production of prostaglandins protect neurons in rodent models of cerebral ischemia and neurodegeneration. Recent studies investigating the functions of selected prostaglandin receptor pathways in mediating COX-2 neurotoxicity have demonstrated both toxic and paradoxically neuroprotective effects of several receptors in models of excitotoxicity. In this study, we investigate the functions of additional prostaglandin receptors not previously characterized in organotypic models of glutamate excitotoxicity. We find that PGD(2), PGI(2), and PGF(2alpha) receptors protect motor neurons in an organotypic spinal cord model of amyotrophic lateral sclerosis (ALS). In addition, PGI(2) and TXA(2) receptors rescue CA1 neurons in an organotypic hippocampal model of N-methyl-d-aspartate excitotoxicity. However, in a model of inflammation induced by lipopolysaccharide, prostaglandin receptors previously found to be protective in excitotoxicity now cause CA1 neuronal death. Taken together, these studies identify novel eicosanoid receptor signaling pathways that mediate neuronal protection in excitotoxic paradigms; these data also support the emerging hypothesis that the toxic/protective effects of eicosanoid signaling on neuronal viability diverge significantly depending on whether excitotoxicity or inflammation predominates as the underlying toxic stimulus. Baltimore, MD 21205, United States. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | 35 | COX | COX-2 | cox 2 | |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | 30 | EP2 | |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | 21 | EP3 | |
| 9600 | PTGFR | prostaglandin F receptor (FP) | 10 | prostaglandin receptor | |
| 9591 | PTGDR | prostaglandin D2 receptor (DP) | 8 | DP1 | |
| 583 | APC | adenomatous polyposis coli | 6 | DP2 | |
| 9593 | PTGER1 | prostaglandin E receptor 1 (subtype EP1), 42kDa | 3 | EP1 | |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | 2 | AKT | |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | 2 | amyloid | |
| 9596 | PTGER4 | prostaglandin E receptor 4 (subtype EP4) | 2 | EP4 | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 1 | iNOS | |
| 4502 | GPR44 | G protein-coupled receptor 44 | 1 | CRTH2 | |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | 1 | COX-1 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | Induction of cyclooxygenase-2 (COX-2) COX-2 with production of prostaglandins occurs in a wide spectrum of |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | Inhibition of the COX-2 pathway and downstream production of prostaglandins protect neurons in rodent |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | investigating the functions of selected prostaglandin receptor pathways in mediating COX-2 neurotoxicity have demonstrated both toxic and paradoxically neuroprotective effects of |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | The inducible isoform of cyclooxygenase COX-2 is rapidly upregulated in vivo in hippocampal and cerebral cortical |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | However in pathologic conditions caused by either excitotoxicity or inflammation COX-2 expression and activity are increased in neurons and glial cells |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | Thus increased COX-2 activity and prostaglandin production are hallmarks of a wide range |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | In humans increased COX-2 and prostaglandin production have been observed in AD ALS multiple |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | Thus COX-2 appears to function physiologically in promoting synaptic activity and pathologically |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | Because inhibition of COX-2 either genetically or pharmacologically decreases neuronal injury in rodent models |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | is considerable interest in defining the downstream mechanisms by which COX-2 exerts its neurotoxicity |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | has been the examination of prostaglandin signaling cascades downstream of COX-2 and the identification of neurotoxic prostaglandin receptors 4 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | the metabolism of arachidonic acid by COX-1 and the inducible COX-2 |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 0.0 | signaling molecules derived from the metabolism of arachidonic acid by COX-1 and the inducible COX-2 |
| 9593 | PTGER1 | prostaglandin E receptor 1 (subtype EP1), 42kDa | EP1 | 0.3 | 2 EP receptor family where there are four subtypes (EP1, EP1 EP2 EP3 and EP4 and for the PGD 2 DP |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | EP receptor family where there are four subtypes (EP1, EP1 EP2 EP3 and EP4 and for the PGD 2 DP family |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | receptor family where there are four subtypes (EP1, EP1 EP2 EP3 and EP4 and for the PGD 2 DP family where |
| 9596 | PTGER4 | prostaglandin E receptor 4 (subtype EP4) | EP4 | 0.3 | receptor family where there are four subtypes (EP1, EP1 EP2 EP3 and EP4 and for the PGD 2 DP family where |
| 9596 | PTGER4 | prostaglandin E receptor 4 (subtype EP4) | EP4 | 0.3 | where there are four subtypes (EP1, EP1 EP2 EP3 and EP4 and for the PGD 2 DP family where there are |
| 9591 | PTGDR | prostaglandin D2 receptor (DP) | DP1 | 1.1 | the PGD 2 DP family where there are two receptors DP1 and DP2 (aka aka CRTH2 |
| 4502 | GPR44 | G protein-coupled receptor 44 | CRTH2 | 1.6 | where there are two receptors DP1 and DP2 (aka aka CRTH2 |
| 583 | APC | adenomatous polyposis coli | DP2 | 0.3 | the PGD 2 DP family where there are two receptors DP1 and DP2 (aka aka CRTH2 |
| 583 | APC | adenomatous polyposis coli | DP2 | 0.2 | 2 DP family where there are two receptors DP1 and DP2 (aka aka CRTH2 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | COX-2 neurotoxicity is presumed to be mediated by one or more |
| 9593 | PTGER1 | prostaglandin E receptor 1 (subtype EP1), 42kDa | EP1 | 0.3 | A toxic effect of the PGE 2 EP1 receptor has been demonstrated in a model of focal ischemia |
| 9593 | PTGER1 | prostaglandin E receptor 1 (subtype EP1), 42kDa | EP1 | 0.3 | has been demonstrated in a model of focal ischemia where EP1 impairs the Na _amp_#x2013 Ca 2 exchange critical in maintaining |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | We have previously reported that the PGE 2 EP2 receptor rescues CA1 pyramidal neurons in organotypic hippocampal cultures treated |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | with NMDA or oxygen glucose deprivation 16 and both the EP2 and EP3 receptors rescue motor neurons in organotypic spinal cord |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | with NMDA or oxygen glucose deprivation 16 and both the EP2 and EP3 receptors rescue motor neurons in organotypic spinal cord |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | or oxygen glucose deprivation 16 and both the EP2 and EP3 receptors rescue motor neurons in organotypic spinal cord slices subjected |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | In vivo the EP2 receptor mediates a significant protective function in models of focal |
| 9591 | PTGDR | prostaglandin D2 receptor (DP) | DP1 | 1.1 | PGD 2 signaling via its DP1 receptor similarly rescues CA1 and CA3 neurons in organotypic hippocampal |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | Mechanistically EP2 and DP1 neuroprotection are dependent on intact cAMP signaling whereas |
| 9591 | PTGDR | prostaglandin D2 receptor (DP) | DP1 | 1.1 | Mechanistically EP2 and DP1 neuroprotection are dependent on intact cAMP signaling whereas EP3 neuroprotection |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | and DP1 neuroprotection are dependent on intact cAMP signaling whereas EP3 neuroprotection is associated with increased AKT phosphorylation 3 and 16 |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | AKT | 0.3 | intact cAMP signaling whereas EP3 neuroprotection is associated with increased AKT phosphorylation 3 and 16 |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | The EP2 receptor neuroprotective in models of glutamate toxicity enhances the inflammatory |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | a murine model of Familial Alzheimer's disease deletion of the EP2 receptor results decreased neuronal lipid peroxidation and A_amp_#x3b2 peptide load |
| 9591 | PTGDR | prostaglandin D2 receptor (DP) | DP1 | 1.1 | PGD 2 and DP1 DP2 IP TP and FP receptor agonists were tested at |
| 583 | APC | adenomatous polyposis coli | DP2 | 0.2 | PGD 2 and DP1 DP2 IP TP and FP receptor agonists were tested at 1 |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | previous studies we determined that PGE 2 signaling via its EP2 and EP3 receptors paradoxically protected motor neurons in a spinal |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | previous studies we determined that PGE 2 signaling via its EP2 and EP3 receptors paradoxically protected motor neurons in a spinal |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | we determined that PGE 2 signaling via its EP2 and EP3 receptors paradoxically protected motor neurons in a spinal cord model |
| 9591 | PTGDR | prostaglandin D2 receptor (DP) | DP1 | 1.1 | protected motor neurons at nM doses selective agonists of the DP1 and DP2 receptors BW245C and DK-PGD 2 respectively also significantly |
| 583 | APC | adenomatous polyposis coli | DP2 | 0.3 | protected motor neurons at nM doses selective agonists of the DP1 and DP2 receptors BW245C and DK-PGD 2 respectively also significantly |
| 583 | APC | adenomatous polyposis coli | DP2 | 0.1 | neurons at nM doses selective agonists of the DP1 and DP2 receptors BW245C and DK-PGD 2 respectively also significantly rescued motor |
| 9591 | PTGDR | prostaglandin D2 receptor (DP) | DP1 | 1.1 | Administration of PGD 2 DP1 DP2 FP IP and TP agonists alone had no effect |
| 583 | APC | adenomatous polyposis coli | DP2 | 0.2 | Administration of PGD 2 DP1 DP2 FP IP and TP agonists alone had no effect on |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | We have previously determined that activation of the PGE 2 EP2 receptor and the PGD 2 DP1 receptor protect CA1 neurons |
| 9591 | PTGDR | prostaglandin D2 receptor (DP) | DP1 | 1.1 | of the PGE 2 EP2 receptor and the PGD 2 DP1 receptor protect CA1 neurons in organotypic hippocampal slices treated with |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | The EP3 agonist sulprostone exerted significant protection at pM_amp_#x2013 nM concentrations ( |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | Administration of EP3 FP IP and TP agonists alone had no effect on |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | Recent studies have demonstrated that the EP2 receptor enhances inflammatory oxidative stress and synaptotoxicity in innate immunity |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | These effects are distinct from the neuroprotective function of the EP2 receptor seen both in vitro in organotypic slices and in |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | We investigated the effect of PGE 2 and the EP2 and EP3 receptors in vitro in a model of LPS |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | We investigated the effect of PGE 2 and the EP2 and EP3 receptors in vitro in a model of LPS |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | investigated the effect of PGE 2 and the EP2 and EP3 receptors in vitro in a model of LPS mediated inflammation |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | Selective activation of the EP2 and EP3 receptors also increased LPS-mediated CA1 neurotoxicity ( Fig |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | Selective activation of the EP2 and EP3 receptors also increased LPS-mediated CA1 neurotoxicity ( Fig |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | Selective activation of the EP2 and EP3 receptors also increased LPS-mediated CA1 neurotoxicity ( Fig 3 B |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | Induction of COX-2 activity and production of downstream prostaglandins is associated in a |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | COX-2 inhibition has been shown to be protective in this in |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | that the DP FP and IP receptors do not mediate COX-2 toxicity in this in vitro model and from our previous |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | in vitro model and from our previous studies 3 the EP2 and EP3 receptors can also be excluded since they too |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | in vitro model and from our previous studies 3 the EP2 and EP3 receptors can also be excluded since they too |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | model and from our previous studies 3 the EP2 and EP3 receptors can also be excluded since they too rescue motor |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | Stimulation of the PGE 2 EP3 receptor with picomolar concentrations of agonist resulted in significant rescue |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | consistent with previous data obtained in spinal cord slices where EP3 activation rescued motor neurons subjected to chronic glutamate toxicity 3 |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | rescued motor neurons subjected to chronic glutamate toxicity 3 here EP3 activation was associated with increased levels of the pro-survival phosphorylated |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | AKT | 0.3 | associated with increased levels of the pro-survival phosphorylated form of AKT |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | dependent on cAMP signaling as is the case for the EP2 and DP1 receptors we hypothesize that this is the case |
| 9591 | PTGDR | prostaglandin D2 receptor (DP) | DP1 | 1.1 | cAMP signaling as is the case for the EP2 and DP1 receptors we hypothesize that this is the case and may |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | In hippocampal slices activation of the EP2 15 and 16 and EP3 ( Fig 2 receptor rescues |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | hippocampal slices activation of the EP2 15 and 16 and EP3 ( Fig 2 receptor rescues CA1 neurons stimulated with NMDA |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | of neurotoxic cytokines and reactive oxygen species stimulation of the EP2 or EP3 receptor now increases LPS-mediated CA1 toxicity |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | cytokines and reactive oxygen species stimulation of the EP2 or EP3 receptor now increases LPS-mediated CA1 toxicity |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | addition of either PGE 2 (10_amp_#x2013;100 10_amp_#x2013 100 nM the EP2 agonist butaprost (200 200 nM or the EP3 agonist sulprostone |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | nM the EP2 agonist butaprost (200 200 nM or the EP3 agonist sulprostone (10 10 nM consistently enhanced LPS-induced CA1 PI |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | The increased toxicity of LPS with addition of EP2/EP3 EP2 EP3 receptor agonists is relevant to recent in vivo studies |
| 9595 | PTGER3 | prostaglandin E receptor 3 (subtype EP3) | EP3 | 0.3 | The increased toxicity of LPS with addition of EP2/EP3 EP2 EP3 receptor agonists is relevant to recent in vivo studies demonstrating |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | For example in the LPS model of innate immunity the EP2 receptor mediates a major component of inflammatory oxidative stress and |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 1.0 | One potential mechanism is via induction of iNOS production of NO and production of reactive oxygen species alternatively |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | In addition in a model of amyloid deposition the EP2 receptor similarly promotes an increase in neuronal |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | In addition in a model of amyloid deposition the EP2 receptor similarly promotes an increase in neuronal lipid peroxidation 13 |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | together these data suggest a dichotomy of function of the EP2 receptor in which the EP2 receptor promotes primary neuroprotection in |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | dichotomy of function of the EP2 receptor in which the EP2 receptor promotes primary neuroprotection in models of glutamate toxicity and |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | dispersed hippocampal neurons are protected from toxicity with application of EP2 receptor agonist suggesting that activation of the neuronal EP2 receptor |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | of EP2 receptor agonist suggesting that activation of the neuronal EP2 receptor promotes a neuroprotective response supporting this is the dependence |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | paracrine synaptic and neuronal injury and genetic ablation of the EP2 receptor in this paradigm is protective 20 |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | The protective function of EP2 signaling in vivo in models of excitotoxicity and cerebral ischemia |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | cerebral ischemia 15 and 16 and the neurotoxic effect of EP2 receptor signaling in the LPS 17 19 and 20 and |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | receptor signaling in the LPS 17 19 and 20 and amyloid models 13 lends support to this hypothesis |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | anti-inflammatory drugs (NSAIDs), NSAIDs which should reduce signaling through the EP2 receptor by decreasing levels of PGE 2 would have similar |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.3 | PGE 2 would have similar effects on neuronal viability as EP2 inhibition alone |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.0 | A larger question is whether COX inhibition by non-steroidal anti-inflammatory drugs (NSAIDs), NSAIDs which should reduce |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 1.0 | In models of in vitro and in vivo excitotoxicity COX-2 inhibition is clearly neuroprotective |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | induction of cyclooxygenase 2 cox 2 with production of prostaglandins occurs in a wide spectrum of acute and chronic neurodegenerative diseases and is associated with neuronal death. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | inhibition of the cox 2 pathway and downstream production of prostaglandins protect neurons in rodent models of cerebral ischemia and neurodegeneration. |
| 9600 | PTGFR | prostaglandin F receptor (FP) | prostaglandin receptor | 1.0 | recent studies investigating the functions of selected prostaglandin receptor pathways in mediating cox 2 neurotoxicity have demonstrated both toxic and paradoxically neuroprotective effects of several receptors in models of excitotoxicity. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | recent studies investigating the functions of selected prostaglandin receptor pathways in mediating cox 2 neurotoxicity have demonstrated both toxic and paradoxically neuroprotective effects of several receptors in models of excitotoxicity. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the inducible isoform of cyclooxygenase cox 2 is rapidly upregulated in vivo in hippocampal and cerebral cortical neurons following n methyl d aspartate nmda receptor dependent synaptic activity [23] consistent with a physiologic role in modulat |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | however in pathologic conditions caused by either excitotoxicity or inflammation cox 2 expression and activity are increased in neurons and glial cells and can promote either primary or secondary neuronal injury respectively. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | thus increased cox 2 activity and prostaglandin production are hallmarks of a wide range neurological disease models including acute excitotoxic events such as cerebral ischemia traumatic brain or spinal cord injury as w |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in humans increased cox 2 and prostaglandin production have been observed in ad als multiple sclerosis and pd [1] [10] [22] and [24] . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | thus cox 2 appears to function physiologically in promoting synaptic activity and pathologically in diseases characterized by excitotoxicity or inflammation. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | because inhibition of cox 2 either genetically or pharmacologically decreases neuronal injury in rodent models of nmda dependent excitotoxicity there is considerable interest in defining the downstream mechanisms by which cox 2 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | either genetically or pharmacologically decreases neuronal injury in rodent models of nmda dependent excitotoxicity there is considerable interest in defining the downstream mechanisms by which cox 2 exerts its neurotoxicity. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | a primary focus has been the examination of prostaglandin signaling cascades downstream of cox 2 and the identification of neurotoxic prostaglandin receptors [4] . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | prostaglandins are lipid signaling molecules derived from the metabolism of arachidonic acid by cox 1 and the inducible cox 2. |
| 9600 | PTGFR | prostaglandin F receptor (FP) | prostaglandin receptor | 1.0 | cox 2 neurotoxicity is presumed to be mediated by one or more of these prostaglandin receptor signaling cascades. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 neurotoxicity is presumed to be mediated by one or more of these prostaglandin receptor signaling cascades. |
| 9600 | PTGFR | prostaglandin F receptor (FP) | prostaglandin receptor | 1.0 | recent studies using genetic models have begun to shed light on the function of prostaglandin receptor signaling in models of neuronal damage. |
| 9600 | PTGFR | prostaglandin F receptor (FP) | prostaglandin receptor | 1.0 | these divergent effects of prostaglandin receptor signaling on neuronal survival occur in models of excitotoxicity where neuronal injury occurs in large part from overactivation of glutamate ionotropic receptors and downstream disruptions in intrace |
| 9600 | PTGFR | prostaglandin F receptor (FP) | prostaglandin receptor | 1.0 | prostaglandin receptor agonists were prepared as a 10 mm stock in 100% ethanol and frozen at _amp_#x2212;70 _amp_#xb0;c until use. |
| 9600 | PTGFR | prostaglandin F receptor (FP) | prostaglandin receptor | 1.0 | slices were then stimulated with 10 _amp_#x3bc;m nmda for 1 h in the presence of prostaglandin receptor agonists or vehicle; after stimulation media was replaced with fresh media containing either receptor agonist or vehicle ethanol _amp_#x2264;0.1% and pi 5 _amp_#x3bc;g/ml for 23 h. |
| 9600 | PTGFR | prostaglandin F receptor (FP) | prostaglandin receptor | 1.0 | taken together these data indicate that additional prostaglandin receptor signaling cascades exert significant neuroprotective effects in excitoxicity. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | induction of cox 2 activity and production of downstream prostaglandins is associated in a wide range of neurological disease models with neuronal injury [9] and [18] . |
| 9600 | PTGFR | prostaglandin F receptor (FP) | prostaglandin receptor | 1.0 | in this study we identify additional prostaglandin receptor signaling pathways that rescue neurons in two organotypic models of excitotoxic neuronal injury. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 inhibition has been shown to be protective in this in vitro model as well as in the transgenic model of familial als [3] [7] and [8] . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | this would suggest that the dp fp and ip receptors do not mediate cox 2 toxicity in this in vitro model and from our previous studies [3] the ep2 and ep3 receptors can also be excluded since they too rescue motor neurons. |
| 9600 | PTGFR | prostaglandin F receptor (FP) | prostaglandin receptor | 1.0 | in a second model using hippocampal slices we have identified three additional prostaglandin receptor signaling pathways that confer neuroprotection in the setting of nmda toxicity. |
| 9600 | PTGFR | prostaglandin F receptor (FP) | prostaglandin receptor | 1.0 | the increased toxicity of lps with addition of ep2/ep3 receptor agonists is relevant to recent in vivo studies demonstrating that in the setting of inflammation prostaglandin receptor signaling can exhibit an opposite and toxic effect on neurons. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in models of in vitro and in vivo excitotoxicity cox 2 inhibition is clearly neuroprotective. |