)| PMID |
15081582 ( ) |
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| Title | Neuroinflammation, COX-2, and ALS--a dual role? |
| Abstract | Although the root cause of many neurodegenerative diseases is unknown, neuroinflammation may play a key role in these types of disease, including amyotrophic lateral sclerosis (ALS). In the context of neurodegeneration, it is unclear if the disease is propagated through inflammation, or whether in contrast, evidence of inflammation reflects an attempt to protect against further cellular injury. Inflammatory pathways involving the cyclooxygenase (COX) enzymes and subsequent generation of prostaglandins are potential target sites for treatments to halt the progression of ALS. In the CNS, COX enzymes are localized to neurons, astrocytes, and microglia and can be induced under various conditions. In addition, there appears to be a dual role for the prostaglandin products of COX enzymes in the nervous system. Some prostaglandins promote the survival of neurons, while others promote apoptosis. In this review, the pathways of COX activity and prostaglandin production form the center of the debate regarding the dual nature of neuroinflammation. We will also discuss how this duality may affect future treatments for neurodegenerative diseases such as ALS. |
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) | 220 | COX | COX-2 | cox 2 | COX-dependent | |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | 14 | COX-1 | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 12 | SOD1 | mSOD1 | SOD1-expressing | superoxide dismutase | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 3 | tumor necrosis factor | TNF | |
| 5973 | IL13 | interleukin 13 | 3 | il 13 | IL-13 | |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | 2 | IL-6 | il 6 | |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | 2 | caspase 3 | |
| 5962 | IL10 | interleukin 10 | 2 | IL-10 | il 10 | |
| 6014 | IL4 | interleukin 4 | 2 | IL-4 | il 4 | |
| 6204 | JUN | jun oncogene | 2 | c jun | c-Jun | |
| 6001 | IL2 | interleukin 2 | 2 | il 2 | IL-2 | |
| 6025 | IL8 | interleukin 8 | 2 | IL-8 | il 8 | |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | 1 | NF-kappaB | |
| 1516 | CAT | catalase | 1 | catalase | |
| 6886 | MAPK9 | mitogen-activated protein kinase 9 | 1 | SAPK | |
| 8723 | SERPINA5 | serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 5 | 1 | protein c inhibitor | |
| 4931 | HLA-A | major histocompatibility complex, class I, A | 1 | MHC | |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | 1 | peroxisome proliferator activated receptor gamma | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 1 | nitric oxide synthase | |
| 6881 | MAPK8 | mitogen-activated protein kinase 8 | 1 | JNK | |
| 8053 | NUDT6 | nudix (nucleoside diphosphate linked moiety X)-type motif 6 | 1 | bFGF | |
| 3676 | FGF2 | fibroblast growth factor 2 (basic) | 1 | basic fibroblast growth factor bfgf | |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | 1 | EP2 | |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | 1 | ICAM-1 | |
| 7808 | NGF | nerve growth factor (beta polypeptide) | 1 | nerve growth factor | |
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 | 0.3 | Inflammatory pathways involving the cyclooxygenase (COX) COX enzymes and subsequent generation of prostaglandins are potential target sites |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | In the CNS COX enzymes are localized to neurons astrocytes and microglia and can |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | to be a dual role for the prostaglandin products of COX enzymes in the nervous system |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | In this review the pathways of COX activity and prostaglandin production form the center of the debate |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | many aspects to neuroinflammation the pathways involving the cyclooxygenase (COX) COX enzyme and subsequent generation of prostaglandins clearly play a role |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | In this review the COX and prostaglandin pathways are used to frame the debate regarding |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | The significance of the COX pathway having both positive and negative outcomes in neurodegenerative disease |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | COX prostaglandins and neuroinflammation |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | Cyclooxygenase (COX) COX is the rate-limiting step in the production of prostaglandins |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | Arachidonic acid is the principal substrate for COX ( O'Banion 1999 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | There are two distinct COX isoenzymes known as COX-1 and COX-2 that are 65% homologous |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 1.3 | There are two distinct COX isoenzymes known as COX-1 and COX-2 that are 65% homologous |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | There are two distinct COX isoenzymes known as COX-1 and COX-2 that are 65% homologous |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | There are two distinct COX isoenzymes known as COX-1 and COX-2 that are 65% homologous |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 1.3 | COX-1 is constitutively expressed in most tissues and produces prostaglandins that |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Conversely COX-2 was initially characterized as an inducible enzyme that is expressed |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | COX-2 is now known to be constitutively expressed in the kidney |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Many cellular factors induce COX-2 expression including multiple growth factors cytokines interleukin (IL)-1_amp_#x3b2; IL -1_amp_#x3b2 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | One transcription factor that influences COX-2 expression following exposure to these cellular factors is NF-_amp_#x3ba B |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | COX-2 has an NF-_amp_#x3ba B binding site in its promoter region |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 0.3 | promoter region that is shared with other inflammatory mediators including ICAM-1 IL-2 IL-8 and complement ( Baldwin 1996 and Schmedtje et |
| 6001 | IL2 | interleukin 2 | IL-2 | 1.3 | region that is shared with other inflammatory mediators including ICAM-1 IL-2 IL-8 and complement ( Baldwin 1996 and Schmedtje et al. |
| 6025 | IL8 | interleukin 8 | IL-8 | 1.3 | that is shared with other inflammatory mediators including ICAM-1 IL-2 IL-8 and complement ( Baldwin 1996 and Schmedtje et al. 1997 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Specific inhibition of COX-2 upregulation can be achieved by factors that inhibit NF-_amp_#x3ba B |
| 6014 | IL4 | interleukin 4 | IL-4 | 1.3 | achieved by factors that inhibit NF-_amp_#x3ba B activity such as IL-4 IL-10 and IL-13 and glucocorticoids ( O'Banion 1999 (see see |
| 5962 | IL10 | interleukin 10 | IL-10 | 1.3 | by factors that inhibit NF-_amp_#x3ba B activity such as IL-4 IL-10 and IL-13 and glucocorticoids ( O'Banion 1999 (see see Table |
| 5973 | IL13 | interleukin 13 | IL-13 | 1.3 | by factors that inhibit NF-_amp_#x3ba B activity such as IL-4 IL-10 and IL-13 and glucocorticoids ( O'Banion 1999 (see see Table |
| 5973 | IL13 | interleukin 13 | IL-13 | 1.3 | that inhibit NF-_amp_#x3ba B activity such as IL-4 IL-10 and IL-13 and glucocorticoids ( O'Banion 1999 (see see Table 1 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | The COX enzymes (COX-1 COX-1 and COX-2 are more completely termed prostaglandin |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 1.3 | The COX enzymes (COX-1 COX-1 and COX-2 are more completely termed prostaglandin G/H G H |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | The COX enzymes (COX-1 COX-1 and COX-2 are more completely termed prostaglandin G/H G H |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | The COX enzymes (COX-1 COX-1 and COX-2 are more completely termed prostaglandin G/H G H synthases (1 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | Next the peroxidase action of the COX enzyme rapidly converts PGG 2 to prostaglandin H (PGH PGH |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | The second peroxidase step of the COX-2 reaction produces the free radical superoxide which may cause damage |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Although it is unlikely that upregulation of COX-2 activity alone produces enough free radicals to account for the |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | Both COX isoforms are detectable in various cell types in the CNS |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | Identification of the patterns of COX enzyme expression will permit us to form a hypothesis regarding |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 1.3 | permit us to form a hypothesis regarding the roles of COX-1 and -2 under normal conditions and during disease |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | permit us to form a hypothesis regarding the roles of COX-1 and -2 under normal conditions and during disease |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | Analysis of the expression of COX isoforms in ALS models is expected to not only determine |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | we will better understand the pathogenic and protective implications of COX activity in ALS |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | COX and neurons |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 1.3 | COX-1 is constitutively expressed throughout the normal brain ( Kawasaki et |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Immunoreactivity for COX-2 is present in the dendritic spines of cortical neurons and |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | display a distinct alteration in the laminar pattern of cortical COX-2 immunoreactivity ( Kaufmann et al. 1996 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | COX-2 immunoreactivity also is observed in the soma and throughout the |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Constitutive COX-2 is in the spinal dorsal and ventral horns as well |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | Indeed the antihyperalgesic activity of COX inhibitors is associated with regulation of constitutive COX-2 in the |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | activity of COX inhibitors is associated with regulation of constitutive COX-2 in the spinal cord ( Svensson and Yaksh 2002 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Although a role for COX-2 in healthy cells is not clear under pathological conditions the |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | cells is not clear under pathological conditions the induction of COX-2 in neurons has been well demonstrated |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | COX-2 was originally localized in neurons using in situ hybridization |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Following a single maximal electroconvulsive seizure COX-2 is rapidly induced in hippocampal and cortical neurons peaking between |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | the N -methyl--aspartic acid (NMDA) NMDA receptor completely inhibits the COX-2 induction implying that NMDA receptor activation is involved in the |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | that NMDA receptor activation is involved in the upregulation of COX-2 in these neurons |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | In addition administration of the glucocorticoid dexamethasone markedly decreases COX-2 induction but only in the neocortex ( Yamagata et al. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | This study suggests that COX-2 upregulation in neurons is dependent upon glutamatergic activity at the |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | basalis can induce seizures in a rat and subsequently upregulate COX-2 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | (1997) 1997 showed that COX-2 induction overlaps with the development of neuronal apoptosis 8 h |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | that precede neuronal death and correlates with the induction of COX-2 mRNA |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | prostaglandin production and subsequent cell death is attenuated by a COX-2 inhibitor but not with a COX-1 selective inhibitor ( Hewett |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 1.3 | is attenuated by a COX-2 inhibitor but not with a COX-1 selective inhibitor ( Hewett et al. 2000 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | In addition genetic studies show that transgenic mice overexpressing COX-2 specifically in neurons are more susceptible to excitotoxicity ( Kelley |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | In contrast COX-2 knockout mice experience reduced neuronal death compared to wild-type mice |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | COX-2 is induced in models of cerebral ischemia |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | but especially the penumbra region show a significant increase in COX-2 mRNA in the ischemic area ipsilateral to the occlusion 4 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | There is a direct correlation between the extent of COX-2 mRNA induction at 4 h and the severity of subsequent |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | the glutamate antagonist agent MK-801 significantly prevents the induction of COX-2 in the penumbra region ( Collaco-Moraes et al. 1996 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | studies provide evidence of a linkage between glutamate activity subsequent COX-2 induction and finally apoptotic death in neurons |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Although increased extracellular glutamate regardless of its source can induce COX-2 in neurons the full consequences of this induction in neurons |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | COX-2 activity correlates with apoptosis in certain models however from studies |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | conducted thus far it is not clear which products of COX-2 induction are contributing to neuronal death which are helping neurons |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | COX and astrocytes |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | In the nervous system COX-2 induction following cell activation or injury is not restricted to |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | injury is not restricted to neurons since astrocytes also upregulate COX-2 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | IL-1_amp_#x3b2 causes a rapid induction of COX-2 peaking at 2 h and returning to baseline by 24 |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 1.3 | There is no correlate change in COX-1 mRNA |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Dexamethasone can attenuate IL-1_amp_#x3b2 -mediated PGE 2 secretion and COX-2 expression ( O'Banion et al. 1996 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Astrocytic COX-2 is also induced by LPS TNF basic fibroblast growth factor |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 1.2 | Astrocytic COX-2 is also induced by LPS TNF basic fibroblast growth factor (bFGF), bFGF and phorbol ester ( |
| 8053 | NUDT6 | nudix (nucleoside diphosphate linked moiety X)-type motif 6 | bFGF | 1.0 | also induced by LPS TNF basic fibroblast growth factor (bFGF), bFGF and phorbol ester ( O'Banion 1999 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Although there is strong evidence for the induction of COX-2 in astrocytes in vitro there are few studies that confirm |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | COX-2 immunoreactive astrocytes have been observed in the hippocampus at 1_amp_#x2013 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | the cortex in Alzheimer's disease in situ hybridization with a COX-2 riboprobe revealed signal in a small proportion of GFAP-positive astrocytes |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | In addition COX-2 colocalizes with GFAP in infarcted human brains ( Sairanen et |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Most in vitro studies are short-term and demonstrate COX-2 induction in the order of hours after the insult |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | vitro models may skew attempts to ascertain the significance of COX-2 activity in neurodegenerative disease |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | In the context of neurodegenerative diseases the chronic induction of COX-2 will be more pathophysiologically relevant |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | COX and microglia |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 1.3 | types in the CNS microglia appear to predominantly express the COX-1 isoform ( Yermakova et al. 1999 |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 1.3 | In addition COX-1 positive microglia accumulate at sites of neuronal degeneration including traumatic |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | The significance of the different isoform of COX expression in this cell type is not clear |
| 4931 | HLA-A | major histocompatibility complex, class I, A | MHC | 0.6 | brain injury by making morphologic changes producing proinflammatory cytokines expressing MHC class II antigens and increasing phagocytosis ( Kreutzberg 1996 and |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | mechanisms than macrophages fibroblasts and synovial cells that can induce COX-2 via the cytokines TNF IL-1_amp_#x3b2 and IL-6 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 1.2 | and synovial cells that can induce COX-2 via the cytokines TNF IL-1_amp_#x3b2 and IL-6 |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.3 | that can induce COX-2 via the cytokines TNF IL-1_amp_#x3b2 and IL-6 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | None of these agents induce COX-2 or NF-_amp_#x3ba B expression in na_amp_#xef ve microglial cells |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | In cultured rat brain microglia LPS induces COX-2 expression that is prevented in the presence of inhibitors of |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.3 | expression that is prevented in the presence of inhibitors of NF-kappaB (dexamethasone, dexamethasone the antioxidant pyrrolidine dithiocarbamate and the protein C |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Thus NF-_amp_#x3ba B is involved in LPS-stimulated microglial COX-2 expression ( Bauer et al. 1997 |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 1.3 | Although increased COX-1 in microglia is observed injury paradigms there are little data |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | injury paradigms there are little data indicating the expression of COX-2 in microglia in vivo |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | (1998) 1998 showed COX-2 immunostaining of cells with a microglial-like morphology in infarcted human |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | After examining the locations and activity of the COX enzymes throughout the CNS a discussion of the potential actions |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | In a carrageenin-induced pleurisy model in rats COX-2 induction peaks at 2 h with maximal PGE 2 production |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | At a later time COX-2 increases again but this time with increased levels of PGD |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | different inflammatory responses are modulated by the addition of a COX-2 inhibitor that causes inhibition of the early inflammatory response but |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | to be a dual role for the products of the COX-2 enzyme in the nervous system |
| 6886 | MAPK9 | mitogen-activated protein kinase 9 | SAPK | 1.3 | apoptotic signals through blocking the activation of stress-activated protein kinase SAPK c-Jun N-terminal kinase (JNK) JNK ( Kawamura et al. 1999 |
| 6204 | JUN | jun oncogene | c-Jun | 0.3 | signals through blocking the activation of stress-activated protein kinase SAPK c-Jun N-terminal kinase (JNK) JNK ( Kawamura et al. 1999 |
| 6881 | MAPK8 | mitogen-activated protein kinase 8 | JNK | 0.3 | activation of stress-activated protein kinase SAPK c-Jun N-terminal kinase (JNK) JNK ( Kawamura et al. 1999 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | In these models inhibition of COX-2 can delay disease onset and progression |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Thus prostaglandin products of COX-2 appear to play a critical role in the development of |
| 9594 | PTGER2 | prostaglandin E receptor 2 (subtype EP2), 53kDa | EP2 | 0.6 | 2 induce apoptosis in a dose-dependent manner likely via the EP2 receptor and subsequent activation of caspase-3 ( Takadera et al. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Addition of COX-2 inhibitors prevents both PGE 2 production and kainic acid-induced neuronal |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | -induced glutamate may lead to further excitatory cell activation and COX-2 induction |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | This mechanism is highlighted in a model of COX-2 overexpression that displays acceleration of glutamate-mediated neuronal apoptosis ( Mirjany |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | of prostaglandins also are different depending upon the presence of COX inhibitors |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Independently these cells are protected from death by the COX-2 inhibitor APHS |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | on cell survival in the presence or absence of a COX-2 inhibitor may be because COX-2 activity results in the generation |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | presence or absence of a COX-2 inhibitor may be because COX-2 activity results in the generation of multiple prostaglandins with potentially |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | When COX-2 is inhibited both the pro- and anti-apoptotic products are lost |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | However when COX-2 is not inhibited multiple prostaglandins are present that can act |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | 2 all can suppress NF-_amp_#x3ba B activation and thus suppress COX-2 induction as well as other inflammatory mediators including inducible nitric |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 1.3 | in which the significance of the differential expression of the COX-1 and COX-2 isoforms may arise |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | in which the significance of the differential expression of the COX-1 and COX-2 isoforms may arise |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | the significance of the differential expression of the COX-1 and COX-2 isoforms may arise |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 1.3 | Since COX-1 increases in activated microglia and is not regulated by NF-_amp_#x3ba |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | microglial origin can regulate the activity of NF-_amp_#x3ba B and COX-2 in adjacent neurons without the same feedback regulation affecting the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.4 | mutations in the cytosolic protein copper_amp_#x2013 zinc superoxide dismutase (SOD1) SOD1 were reported in several FALS families |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.4 | Since then over 95 mutations in SOD1 have been identified in patients with FALS ( Mithal et |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.4 | SOD1 is a metalloenzyme that detoxifies the superoxide anion to form |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.4 | However SOD1 mutations account for only 20% of familial ALS ( Feldman |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.4 | Because mutant SOD1 explains only a very small subset of ALS pathology it |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | COX prostaglandins and ALS |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | COX-2 activity appears to play an important role in ALS |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | In many different models COX-2 upregulation occurs concurrently with ALS disease events |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | COX-2 and PGE 2 are significantly elevated upwards of sevenfold in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-expressing | 1.4 | In the spinal cords of transgenic mutant human SOD1-expressing (mSOD1) mSOD1 mice there is increased expression of COX-2 but |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.4 | In the spinal cords of transgenic mutant human SOD1-expressing (mSOD1) mSOD1 mice there is increased expression of COX-2 but not COX-1 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | human SOD1-expressing (mSOD1) mSOD1 mice there is increased expression of COX-2 but not COX-1 mRNA |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 1.3 | mSOD1 mice there is increased expression of COX-2 but not COX-1 mRNA |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | COX-2 mRNA and protein levels COX catalytic activity and PGE 2 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | COX-2 mRNA and protein levels COX catalytic activity and PGE 2 levels are all increased in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.4 | increased in the spinal cord but not the cerebellum of mSOD1 mice |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | COX-2 levels in mSOD1 mice are increased in both early symptomatic |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.4 | COX-2 levels in mSOD1 mice are increased in both early symptomatic and end-stage disease |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Selective inhibition of COX-2 with SC236 protects motor neurons in an organotypic cell culture |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | In addition several drugs that inhibit COX isoforms directly prevent the death of motor neurons in enriched |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | This suggests that the motor neurons activate COX during an injury and the mechanisms of protection by COX |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | COX during an injury and the mechanisms of protection by COX inhibitors in mixed culture or in vivo is not mediated |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.4 | In the transgenic mSOD1 mouse the nonselective COX inhibitor acetylsalicylate delays the appearance of |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | In the transgenic mSOD1 mouse the nonselective COX inhibitor acetylsalicylate delays the appearance of motor deficits ( Barneoud |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | This delayed onset is recapitulated when the selective COX-2 inhibitor nimesulide is administered prophylactically in these mice ( Pompl |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Treatment with Celecoxib a different selective COX-2 inhibitor also prolongs survival in the mSOD1 mouse model of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.4 | a different selective COX-2 inhibitor also prolongs survival in the mSOD1 mouse model of ALS ( Drachman et al. 2002 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | It seems that neuroinflammation proceeds albeit more slowly in COX-2 inhibitor-treated animals possibly through the slower microglial COX-1 upregulation and |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 1.3 | slowly in COX-2 inhibitor-treated animals possibly through the slower microglial COX-1 upregulation and likely through multiple additional regulatory mechanisms |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Experiments that demonstrate protective abilities of COX-2 inhibition imply that COX-2 activation contributes to neuronal vulnerability and |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Experiments that demonstrate protective abilities of COX-2 inhibition imply that COX-2 activation contributes to neuronal vulnerability and apoptosis by an undefined |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-dependent | 0.0 | It may be that the COX-dependent production of reactive oxygen species during the peroxidase step of |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | not known whether the amount of ROS produced by the COX enzyme is sufficient to cause neuronal death |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | In addition some of the prostaglandin products of the COX-2 enzyme cause direct damage to neurons as well as act |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | It is clear that neuroinflammation particularly COX-2 upregulation and prostaglandin production plays a significant role in neurodegenerative |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | It seems likely that COX-2 inhibitors can delay the progression of symptoms and clinical studies |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Although treatment of neurodegenerative diseases such as ALS with COX-2 inhibitors is likely to produce some symptomatic benefit it is |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | activate NF-_amp_#x3ba B leading to a paradoxical activation of the COX-2 enzyme that is clearly a problem for this therapeutic approach |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | prostaglandins that feedback on NF-_amp_#x3ba B to regulate transcription of COX-2 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Certain downstream products of the COX-2 enzyme are pro-apoptotic while others are neuroprotective |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | Inhibiting COX-2 will block both the neurodegenerative and neuroprotective products of this |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | in the development of future therapies rather than broadly targeting COX-2 or even further upstream at the level of NF-_amp_#x3ba B |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 3.8 | of NF-_amp_#x3ba B to target specific prostaglandin synthases downstream of COX-2 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | Thorough understanding of the individual roles of prostaglandins COX isoforms and neuroprotective mechanisms of COX inhibitors are essential to |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.3 | individual roles of prostaglandins COX isoforms and neuroprotective mechanisms of COX inhibitors are essential to further these therapeutic developments |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | there are two distinct cox isoenzymes known as cox 1 and cox 2 that are 65% homologous. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | conversely cox 2 was initially characterized as an inducible enzyme that is expressed in response to inflammatory stimuli cytokines and mitogens o'banion 1999 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 is now known to be constitutively expressed in the kidney stomach and central nervous system hoffmann 2000 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | many cellular factors induce cox 2 expression including multiple growth factors cytokines interleukin il 1_amp_#x3b2; tumor necrosis factor tnf lipopolysaccharide lps phorbol ester and elevated intracellular calcium concentration. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor | 1.0 | many cellular factors induce cox 2 expression including multiple growth factors cytokines interleukin il 1_amp_#x3b2; tumor necrosis factor tnf lipopolysaccharide lps phorbol ester and elevated intracellular calcium concentration. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | one transcription factor that influences cox 2 expression following exposure to these cellular factors is nf _amp_#x3ba;b. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 has an nf _amp_#x3ba;b binding site in its promoter region that is shared with other inflammatory mediators including icam 1 il 2 il 8 and complement baldwin 1996 and schmedtje et al. 1997 . |
| 6001 | IL2 | interleukin 2 | il 2 | 1.0 | cox 2 has an nf _amp_#x3ba;b binding site in its promoter region that is shared with other inflammatory mediators including icam 1 il 2 il 8 and complement baldwin 1996 and schmedtje et al. 1997 . |
| 6025 | IL8 | interleukin 8 | il 8 | 1.0 | cox 2 has an nf _amp_#x3ba;b binding site in its promoter region that is shared with other inflammatory mediators including icam 1 il 2 il 8 and complement baldwin 1996 and schmedtje et al. 1997 . |
| 5962 | IL10 | interleukin 10 | il 10 | 1.0 | specific inhibition of cox 2 upregulation can be achieved by factors that inhibit nf _amp_#x3ba;b activity such as il 4 il 10 and il 13 and glucocorticoids o'banion 1999 see table 1 . |
| 5973 | IL13 | interleukin 13 | il 13 | 1.0 | specific inhibition of cox 2 upregulation can be achieved by factors that inhibit nf _amp_#x3ba;b activity such as il 4 il 10 and il 13 and glucocorticoids o'banion 1999 see table 1 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | specific inhibition of cox 2 upregulation can be achieved by factors that inhibit nf _amp_#x3ba;b activity such as il 4 il 10 and il 13 and glucocorticoids o'banion 1999 see table 1 . |
| 6014 | IL4 | interleukin 4 | il 4 | 1.0 | specific inhibition of cox 2 upregulation can be achieved by factors that inhibit nf _amp_#x3ba;b activity such as il 4 il 10 and il 13 and glucocorticoids o'banion 1999 see table 1 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the cox enzymes cox 1 and cox 2 are more completely termed prostaglandin g/h synthases 1 and 2 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the second peroxidase step of the cox 2 reaction produces the free radical superoxide which may cause damage to cells in als and other neurodegenerative diseases kaufmann et al. 1996 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | although it is unlikely that upregulation of cox 2 activity alone produces enough free radicals to account for the degree of oxidative damage associated with neurodegenerative diseases it may be one of several sources that together cause significant |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | immunoreactivity for cox 2 is present in the dendritic spines of cortical neurons and thus may be involved in synaptic signaling kaufmann et al. 1996 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | these rats display a distinct alteration in the laminar pattern of cortical cox 2 immunoreactivity kaufmann et al. 1996 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 immunoreactivity also is observed in the soma and throughout the dendritic extent of many neurons kaufmann et al. 1996 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | constitutive cox 2 is in the spinal dorsal and ventral horns as well as in dorsal root ganglia yaksh et al. 2001 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | indeed the antihyperalgesic activity of cox inhibitors is associated with regulation of constitutive cox 2 in the spinal cord svensson and yaksh 2002 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | although a role for cox 2 in healthy cells is not clear under pathological conditions the induction of cox 2 in neurons has been well demonstrated. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 was originally localized in neurons using in situ hybridization. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | following a single maximal electroconvulsive seizure cox 2 is rapidly induced in hippocampal and cortical neurons peaking between 1 and 2 h and falling to baseline by 24 h. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | administration of mk 801 an antagonist of the n methyl aspartic acid nmda receptor completely inhibits the cox 2 induction implying that nmda receptor activation is involved in the upregulation of cox 2 in these neurons. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in addition administration of the glucocorticoid dexamethasone markedly decreases cox 2 induction but only in the neocortex yamagata et al. 1993 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | this study suggests that cox 2 upregulation in neurons is dependent upon glutamatergic activity at the synapse. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | intraperitoneal administration of kainic acid and also its local injection into the nuclear basalis can induce seizures in a rat and subsequently upregulate cox 2. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | 1997 showed that cox 2 induction overlaps with the development of neuronal apoptosis 8 h following seizure induction. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | furthermore exposure of mixed cortical cells in vitro to nmda elicits a time dependent accumulation of prostaglandins that precede neuronal death and correlates with the induction of cox 2 mrna. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | this nmda stimulated prostaglandin production and subsequent cell death is attenuated by a cox 2 inhibitor but not with a cox 1 selective inhibitor hewett et al. 2000 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in addition genetic studies show that transgenic mice overexpressing cox 2 specifically in neurons are more susceptible to excitotoxicity kelley et al. 1999 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in contrast cox 2 knockout mice experience reduced neuronal death compared to wild type mice when exposed to nmda or ischemia iadecola et al. 2001 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 is induced in models of cerebral ischemia. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | both regions but especially the penumbra region show a significant increase in cox 2 mrna in the ischemic area ipsilateral to the occlusion 4 and 24 h following the occlusion. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | there is a direct correlation between the extent of cox 2 mrna induction at 4 h and the severity of subsequent tissue damage. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | also the glutamate antagonist agent mk 801 significantly prevents the induction of cox 2 in the penumbra region collaco moraes et al. 1996 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | these studies provide evidence of a linkage between glutamate activity subsequent cox 2 induction and finally apoptotic death in neurons. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | although increased extracellular glutamate regardless of its source can induce cox 2 in neurons the full consequences of this induction in neurons are still unclear. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 activity correlates with apoptosis in certain models; however from studies conducted thus far it is not clear which products of cox 2 induction are contributing to neuronal death which are helping neurons to escape death or which are unrelated to cell death. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in the nervous system cox 2 induction following cell activation or injury is not restricted to neurons since astrocytes also upregulate cox 2. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | il 1_amp_#x3b2; causes a rapid induction of cox 2 peaking at 2 h and returning to baseline by 24 h. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | dexamethasone can attenuate il 1_amp_#x3b2; mediated pge 2 secretion and cox 2 expression o'banion et al. 1996 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | astrocytic cox 2 is also induced by lps tnf basic fibroblast growth factor bfgf and phorbol ester o'banion 1999 . |
| 3676 | FGF2 | fibroblast growth factor 2 (basic) | basic fibroblast growth factor bfgf | 1.0 | astrocytic cox 2 is also induced by lps tnf basic fibroblast growth factor bfgf and phorbol ester o'banion 1999 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | although there is strong evidence for the induction of cox 2 in astrocytes in vitro there are few studies that confirm this finding in vivo. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 immunoreactive astrocytes have been observed in the hippocampus at 1_amp_#x2013;11 weeks but not 3 days following kainic acid seizure induction in rats sandhya et al. 1998 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in the cortex in alzheimer's disease in situ hybridization with a cox 2 riboprobe revealed signal in a small proportion of gfap positive astrocytes chang et al. 1996 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in addition cox 2 colocalizes with gfap in infarcted human brains sairanen et al. 1998 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | most in vitro studies are short term and demonstrate cox 2 induction in the order of hours after the insult. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | thus the in vitro models may skew attempts to ascertain the significance of cox 2 activity in neurodegenerative disease. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in the context of neurodegenerative diseases the chronic induction of cox 2 will be more pathophysiologically relevant. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | microglia have different regulatory mechanisms than macrophages fibroblasts and synovial cells that can induce cox 2 via the cytokines tnf il 1_amp_#x3b2; and il 6. |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | microglia have different regulatory mechanisms than macrophages fibroblasts and synovial cells that can induce cox 2 via the cytokines tnf il 1_amp_#x3b2; and il 6. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | none of these agents induce cox 2 or nf _amp_#x3ba;b expression in na_amp_#xef;ve microglial cells. |
| 8723 | SERPINA5 | serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 5 | protein c inhibitor | 1.0 | in cultured rat brain microglia lps induces cox 2 expression that is prevented in the presence of inhibitors of nf kappab dexamethasone the antioxidant pyrrolidine dithiocarbamate and the protein c inhibitor go6976 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in cultured rat brain microglia lps induces cox 2 expression that is prevented in the presence of inhibitors of nf kappab dexamethasone the antioxidant pyrrolidine dithiocarbamate and the protein c inhibitor go6976 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | thus nf _amp_#x3ba;b is involved in lps stimulated microglial cox 2 expression bauer et al. 1997 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | although increased cox 1 in microglia is observed injury paradigms there are little data indicating the expression of cox 2 in microglia in vivo. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | 1998 showed cox 2 immunostaining of cells with a microglial like morphology in infarcted human brain but did not show colocalization with microglial markers. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in a carrageenin induced pleurisy model in rats cox 2 induction peaks at 2 h with maximal pge 2 production and an increasing inflammatory response. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | at a later time cox 2 increases again but this time with increased levels of pgd 2 and pgj 2 and decreased inflammation. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | these temporally different inflammatory responses are modulated by the addition of a cox 2 inhibitor that causes inhibition of the early inflammatory response but increased inflammation later gilroy et al. 1999 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | there also appears to be a dual role for the products of the cox 2 enzyme in the nervous system. |
| 7808 | NGF | nerve growth factor (beta polypeptide) | nerve growth factor | 1.0 | in addition pge 1 also derived from pge 2 reduces the incidence of apoptotic death in nerve growth factor deprived pheochromocytoma pc12 cells by preventing the activation of apoptotic signals through blocking the activation of stress activated protein kinase sapk /c jun n terminal kinase jnk kawamura et |
| 6204 | JUN | jun oncogene | c jun | 1.0 | apoptotic death in nerve growth factor deprived pheochromocytoma pc12 cells by preventing the activation of apoptotic signals through blocking the activation of stress activated protein kinase sapk /c jun n terminal kinase jnk kawamura et al. 1999 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in these models inhibition of cox 2 can delay disease onset and progression. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | thus prostaglandin products of cox 2 appear to play a critical role in the development of motor neuron degeneration almer et al. 2002 . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | in rat cortical cells high concentrations of pge 2 induce apoptosis in a dose dependent manner likely via the ep2 receptor and subsequent activation of caspase 3 takadera et al. 2002 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | addition of cox 2 inhibitors prevents both pge 2 production and kainic acid induced neuronal death in these cells kim et al. 2002 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the pge 2 stimulated glutamate release produces a feed forward cycle whereby pge 2 induced glutamate may lead to further excitatory cell activation and cox 2 induction. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | this mechanism is highlighted in a model of cox 2 overexpression that displays acceleration of glutamate mediated neuronal apoptosis mirjany et al. 2002 . |
| 9236 | PPARG | peroxisome proliferator-activated receptor gamma | peroxisome proliferator activated receptor gamma | 1.0 | another prostaglandin 15 deoxy_amp_#x394; 12 14 pgj 2 a natural peroxisome proliferator activated receptor gamma ligand formed from pgd 2 induces apoptosis in both human astrocytes chattopadhyay et al. 2000 and cortical neurons rohn et al. 2001 . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | exposure to pgd 2 synthase induces apoptosis in pc12 neuronal cells via caspase 3 activation. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | independently these cells are protected from death by the cox 2 inhibitor aphs. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | one possible reason why there are differential effects on cell survival in the presence or absence of a cox 2 inhibitor may be because cox 2 activity results in the generation of multiple prostaglandins with potentially different effects. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | when cox 2 is inhibited both the pro and anti apoptotic products are lost so cellular responses are directly produced by any single prostaglandin added to culture media. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | however when cox 2 is not inhibited multiple prostaglandins are present that can act in a synergistic or antagonistic manner. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | prostaglandins pga 1 pga 2 and pgj 2 all can suppress nf _amp_#x3ba;b activation and thus suppress cox 2 induction as well as other inflammatory mediators including inducible nitric oxide synthase and certain cytokines. |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | prostaglandins pga 1 pga 2 and pgj 2 all can suppress nf _amp_#x3ba;b activation and thus suppress cox 2 induction as well as other inflammatory mediators including inducible nitric oxide synthase and certain cytokines. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | interestingly this is one area in which the significance of the differential expression of the cox 1 and cox 2 isoforms may arise. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | since cox 1 increases in activated microglia and is not regulated by nf _amp_#x3ba;b then prostaglandins of microglial origin can regulate the activity of nf _amp_#x3ba;b and cox 2 in adjacent neurons without the same feedback regulation affecting the microglia. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | in 1993 mutations in the cytosolic protein copper_amp_#x2013;zinc superoxide dismutase sod1 were reported in several fals families. |
| 1516 | CAT | catalase | catalase | 1.0 | sod1 is a metalloenzyme that detoxifies the superoxide anion to form hydrogen peroxide which is then converted to water through the activity of another enzyme such as catalase mithal et al. 1999 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 activity appears to play an important role in als. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in many different models cox 2 upregulation occurs concurrently with als disease events. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 and pge 2 are significantly elevated upwards of sevenfold in postmortem spinal cords of patients with sporadic als almer et al. 2001 and yasojima et al. 2001 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in the spinal cords of transgenic mutant human sod1 expressing msod1 mice there is increased expression of cox 2 but not cox 1 mrna. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 mrna and protein levels cox catalytic activity and pge 2 levels are all increased in the spinal cord but not the cerebellum of msod1 mice. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 levels in msod1 mice are increased in both early symptomatic and end stage disease in neurons and to a lesser extent in astrocytes in the anterior horn of the spinal cord. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | selective inhibition of cox 2 with sc236 protects motor neurons in an organotypic cell culture model of als drachman and rothstein 2000 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | this delayed onset is recapitulated when the selective cox 2 inhibitor nimesulide is administered prophylactically in these mice pompl et al. 2003 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | treatment with celecoxib a different selective cox 2 inhibitor also prolongs survival in the msod1 mouse model of als drachman et al. 2002 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | it seems that neuroinflammation proceeds albeit more slowly in cox 2 inhibitor treated animals possibly through the slower microglial cox 1 upregulation and likely through multiple additional regulatory mechanisms. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | experiments that demonstrate protective abilities of cox 2 inhibition imply that cox 2 activation contributes to neuronal vulnerability and apoptosis by an undefined mechanism or mechanisms. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in addition some of the prostaglandin products of the cox 2 enzyme cause direct damage to neurons as well as act in both an autocrine and paracrine manner to propagate inflammation. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | it is clear that neuroinflammation particularly cox 2 upregulation and prostaglandin production plays a significant role in neurodegenerative disorders such as als. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | it seems likely that cox 2 inhibitors can delay the progression of symptoms and clinical studies addressing this issue are both warranted and currently underway. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | although treatment of neurodegenerative diseases such as als with cox 2 inhibitors is likely to produce some symptomatic benefit it is very unlikely that these drugs will revolutionize the treatment of neurodegenerative disease. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in fact it is reported that high doses of certain nsaids can activate nf _amp_#x3ba;b leading to a paradoxical activation of the cox 2 enzyme that is clearly a problem for this therapeutic approach niederberger et al. 2001 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | this finding is not surprising given that it is the level of prostaglandins that feedback on nf _amp_#x3ba;b to regulate transcription of cox 2. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | certain downstream products of the cox 2 enzyme are pro apoptotic while others are neuroprotective. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | inhibiting cox 2 will block both the neurodegenerative and neuroprotective products of this enzyme. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | it may be more appropriate in the development of future therapies rather than broadly targeting cox 2 or even further upstream at the level of nf _amp_#x3ba;b to target specific prostaglandin synthases downstream of cox 2. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | or even further upstream at the level of nf _amp_#x3ba;b to target specific prostaglandin synthases downstream of cox 2. |