)| PMID |
15453089 ( ) |
|---|---|
| Title | Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. |
| Abstract | Cyclooxygenase (COX) catalyses the first committed step in the synthesis of prostanoids, a large family of arachidonic acid metabolites comprising prostaglandins, prostacyclin, and thromboxanes, and is a major target of non-steroidal anti-inflammatory drugs (NSAIDs). COX exists as constitutive and inducible isoforms. COX-2 is the inducible isoform, rapidly expressed in several cell types in response to growth factors, cytokines, and pro-inflammatory molecules. Since its discovery in the early 1990s, COX-2 has emerged as a major player in inflammatory reactions in peripheral tissues. By extension, COX-2 expression in brain has been associated with pro-inflammatory activities, thought to be instrumental in neurodegenerative processes of several acute and chronic diseases. However, 2 major aspects should be borne in mind. First, in the central nervous system, COX-2 is expressed under normal conditions and contributes to fundamental brain functions, such as synaptic activity, memory consolidation, and functional hyperemia. Second, "neuroinflammation" is a much more controlled reaction than inflammation in peripheral tissues, and in many cases is triggered and sustained by activation of resident cells, particularly microglia. In spite of the intense research of the last decade, the evidence of a direct role of COX-2 in neurodegenerative events is still controversial. This article will review new data in this area, focusing on some major human neurological diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson disease, Creutzfeldt-Jakob disease, and Alzheimer disease. Furthermore, the emerging role of COX-2 in behavioral and cognitive functions will be discussed. Sanita, Viale Regina Elena 299, 00161 Rome, Italy. luisa.minghetti@iss.it |
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) | 312 | COX-independent | COX-2 | cox 2 | COX-2-specific | COX2 | COX-2-derived | COX-derived | COX-2-positive | COX-2-inhibitor | |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | 45 | COX-1 | COX-1-positive | PCOX-1 | COX-3 | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 6 | SOD1 | |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | 4 | amyloid | |
| 1325 | C4BPA | complement component 4 binding protein, alpha | 4 | PrP | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 3 | iNOS | |
| 1033 | BDNF | brain-derived neurotrophic factor | 3 | BDNF | BDNF-associated | |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | 2 | IL-6 | il 6 | |
| 5992 | IL1B | interleukin 1, beta | 2 | IL-1 | il 1 | |
| 11765 | TGFA | transforming growth factor, alpha | 1 | transforming growth factor | |
| 24692 | FCAMR | Fc receptor, IgA, IgM, high affinity | 1 | fc receptor | |
| 6925 | MBP | myelin basic protein | 1 | myelin basic protein | |
| 9449 | PRNP | prion protein (p27-30) (Creutzfeldt-Jakob disease, Gerstmann-Strausler-Scheinker syndrome, fatal familial insomnia) | 1 | prion protein prp | |
| 3613 | FCGR1A | Fc fragment of IgG, high affinity Ia, receptor (CD64) | 1 | CD64 | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 1 | TNF- | |
| 5438 | IFNG | interferon, gamma | 1 | IFN- | |
| 1582 | CCND1 | cyclin D1 | 1 | cyclin d1 | |
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 | 0.6 | Cyclooxygenase (COX) COX catalyses the first committed step in the synthesis of prostanoids |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | COX exists as constitutive and inducible isoforms |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | COX-2 is the inducible isoform rapidly expressed in several cell types |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Since its discovery in the early 1990s COX-2 has emerged as a major player in inflammatory reactions in |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | By extension COX-2 expression in brain has been associated with pro-inflammatory activities thought |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | First in the central nervous system COX-2 is expressed under normal conditions and contributes to fundamental brain |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | the last decade the evidence of a direct role of COX-2 in neurodegenerative events is still controversial |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Furthermore the emerging role of COX-2 in behavioral and cognitive functions will be discussed |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | Cyclooxygenase (COX), COX also known as prostaglandin (PG) PG H synthase catalyses the |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | COX has become a very popular enzyme since 1971 when it |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | (NSAIDs) NSAIDs exert their anti-inflammatory properties through the inhibition of COX enzymatic activity thus preventing PG synthesis ( 1 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | class of drugs affects many other important cellular targets nonetheless COX remains central to the development of anti-inflammatory treatments of a |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | COX is a unique enzyme |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | production of free radicals which are in part utilized by COX itself ( Fig 1 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | two enzymatic activities occur at distinct interacting sites on the COX molecule and external factors can affect each of them independently |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | Second during the cyclooxygenase activity COX undergoes a conformational rearrangement leading to an unstable intermediate which |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | COX is an integral membrane glycoprotein consisting of a homodimer with |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | Besides a constitutive isoform (COX-1), COX-1 which is widely distributed in virtually all cell types and |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | to mediate physiological responses a second and inducible isoform termed COX-2 was identified in the early 1990s ( 4 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | COX-2 is rapidly expressed in several cell types in response to |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | COX-1 and COX-2 are coded by 2 distinct genes located on |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | COX-1 and COX-2 are coded by 2 distinct genes located on |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | COX-1 and COX-2 are coded by 2 distinct genes located on human chromosome |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | The COX-2 gene is characterized by the presence of a TATA box |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | its promoter region which account for the complex regulation of COX-2 expression |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | determinant or as translation inhibitory element suggesting post-transcriptional control of COX-2 expression |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | On the contrary the COX-1 gene represents a classical _amp_#147 housekeeping_amp_#148 gene lacking of a |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | 2 isoenzymes which could account for the different sensitivities of COX-1 and COX-2 to specific inhibitors ( 5 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | 2 isoenzymes which could account for the different sensitivities of COX-1 and COX-2 to specific inhibitors ( 5 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | which could account for the different sensitivities of COX-1 and COX-2 to specific inhibitors ( 5 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | the 2 isoforms is the 18-amino acid insert near the COX-2 C-terminus which is not present in COX-1 and has allowed |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | insert near the COX-2 C-terminus which is not present in COX-1 and has allowed the production of specific antibodies |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | The distribution of the 2 COX isoforms has been extensively studied in rat and human tissues |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | In the majority of the tissues COX-1 appears to be the only isoform constitutively expressed confirming the |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | However in brain testes and kidney macula densa cells both COX-1 and COX-2 are expressed under physiological conditions ( 2 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | However in brain testes and kidney macula densa cells both COX-1 and COX-2 are expressed under physiological conditions ( 2 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | brain testes and kidney macula densa cells both COX-1 and COX-2 are expressed under physiological conditions ( 2 |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | In rat brain COX-1 and COX-2 immunoreactivities are present in discrete neuronal populations distributed |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | In rat brain COX-1 and COX-2 immunoreactivities are present in discrete neuronal populations distributed |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | In rat brain COX-1 and COX-2 immunoreactivities are present in discrete neuronal populations distributed in distinct |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | In other regions such as midbrain pons and medulla COX-1 immunoreactivity prevails ( 6 7 |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | Similarly mRNAs for both COX-1 and COX-2 are present in several regions of human brain |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Similarly mRNAs for both COX-1 and COX-2 are present in several regions of human brain |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Similarly mRNAs for both COX-1 and COX-2 are present in several regions of human brain although COX-2 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | COX-2 are present in several regions of human brain although COX-2 is the prominent isoform particularly in the hippocampus ( 8 |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | The relative contribution of COX-1 and COX-2 activity to brain pathology and physiology has been |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | The relative contribution of COX-1 and COX-2 activity to brain pathology and physiology has been |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | The relative contribution of COX-1 and COX-2 activity to brain pathology and physiology has been recently questioned |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | On one side it has been argued that COX-1 activity in brain diseases has been overlooked on the other |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | been overlooked on the other side mandatory evidence suggests that COX-2 plays a special role in normal neuronal function and in |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | studies it is clear that the popular paradigm by which COX-1 serves physiological functions and COX-2 is responsible for _amp_#147 pathological_amp_#148 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | the popular paradigm by which COX-1 serves physiological functions and COX-2 is responsible for _amp_#147 pathological_amp_#148 PGs cannot explain an increasing |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | Recently a third variant of COX named COX-3 and 2 partial COX-1 proteins (PCOX-1 PCOX-1 proteins |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-3 | 0.3 | Recently a third variant of COX named COX-3 and 2 partial COX-1 proteins (PCOX-1 PCOX-1 proteins have been |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX2 | 1.8 | Recently a third variant of COX named COX-3 and 2 partial COX-1 proteins (PCOX-1 PCOX-1 proteins have been |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | a third variant of COX named COX-3 and 2 partial COX-1 proteins (PCOX-1 PCOX-1 proteins have been identified from canine and |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | PCOX-1 | 0.8 | of COX named COX-3 and 2 partial COX-1 proteins (PCOX-1 PCOX-1 proteins have been identified from canine and human cerebral cortex |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-3 | 0.3 | COX-3 and one of the PCOX-1 are products of the COX-1 |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | PCOX-1 | 0.8 | COX-3 and one of the PCOX-1 are products of the COX-1 gene but retain intron 1 |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | COX-3 and one of the PCOX-1 are products of the COX-1 gene but retain intron 1 in their mRNA |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | in the in cerebral cortex where the expression of the COX-1 variant gene accounts for ~5_amp_#37 of COX-1 |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | expression of the COX-1 variant gene accounts for ~5_amp_#37 of COX-1 |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | As its counterpart COX-1 COX-3 is not induced by acute inflammatory stimulation ( 13 |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-3 | 0.3 | As its counterpart COX-1 COX-3 is not induced by acute inflammatory stimulation ( 13 |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-3 | 0.3 | COX-3 but not PCOX-1 exhibits enzymatic activity that is glycosylation-dependent and |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | PCOX-1 | 0.8 | COX-3 but not PCOX-1 exhibits enzymatic activity that is glycosylation-dependent and especially sensitive to |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-3 | 0.3 | Thus COX-3 could represent the brain-specific COX isoform the existence of which |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | Thus COX-3 could represent the brain-specific COX isoform the existence of which was hypothesized a few decades |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | of paracetamol in spite of its poor ability to inhibit COX from peripheral tissues ( 12 |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-3 | 0.3 | Nonetheless the functional role of COX-3 is largely unknown and more intense research is required to |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-3 | 0.3 | more intense research is required to elucidate the contribution of COX-3 to the overall PG production in brain |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | The potential role of COX isoforms and PGs in brain diseases has been extensively reviewed |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Over-expression of COX-2 has been associated with neurotoxicity in acute conditions such as |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | However the beneficial or detrimental role played by COX-2 in inflammatory and neurodegenerative brain pathologies is still controversial |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | First the emerging role of COX-2 in cognitive functions will be discussed since understanding the role |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | cognitive functions will be discussed since understanding the role of COX-2 in brain function is an important prerequisite to fully understanding |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | to fully understanding how to exploit the potential benefits of COX-2 inhibition in disabling neurological diseases |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | In mammalian brain COX-2 is constitutively expressed in specific neuronal populations under normal physiological |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | In rat brain COX-2 mRNA and immunoreactivity were detected in dentate gyrus granule cells |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | This _amp_#147 constitutive_amp_#148 neuronal COX-2 expression should be more correctly regarded as _amp_#147 dynamically_amp_#148 regulated |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | The dependence of COX-2 expression on natural excitatory synaptic activity is supported by the |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | natural excitatory synaptic activity is supported by the presence of COX-2 immunoreactivity in distal dendrites and dendritic spines which are involved |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | distribution within a neuronal population is compatible with induction of COX-2 in subsets of neurons in response to natural excitatory synaptic |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | The involvement of COX-2 in synaptic activity is further supported by the developmental profile |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | synaptic activity is further supported by the developmental profile of COX-2 expression |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | In rat brain COX-2 expression follows developmental gradients and coincides with the critical period |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | and abnormalities of dendritic branching_amp_#151 the laminar pattern of cortical COX-2 immunoreactivity is disrupted in that COX-2-positive neurons are decreased in |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2-positive | 0.0 | laminar pattern of cortical COX-2 immunoreactivity is disrupted in that COX-2-positive neurons are decreased in number and randomly distributed ( 18 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | neurons during the first post-natal week showed decreased levels of COX-2 but not COX-1 in the hippocampus at adulthood |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | first post-natal week showed decreased levels of COX-2 but not COX-1 in the hippocampus at adulthood |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | of hippocampal cholinergic input may impact on the expression of COX-2 in hippocampal neurons and on the functional role of PGs |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Indirect evidence of COX-2 involvement in synaptic plasticity has been obtained in the recent |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | plasticity has been obtained in the recent years by using COX inhibitors in in vivo and in vitro models of synaptic |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | COX-2 inhibitors but not COX-1 selective inhibitors administered systemically shortly after |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | COX-2 inhibitors but not COX-1 selective inhibitors administered systemically shortly after training in the Morris |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | Similarly intracerebral injection of COX inhibitors in chicks attenuated memory of a passive avoidance response |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2-specific | 1.8 | In addition pre-training infusion of a COX-2-specific inhibitor (celecoxib) celecoxib in the hippocampus of adult rats impaired |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | acquisition of the Morris water maze suggesting that in rats COX-2 activity in the hippocampus is necessary for both memory and |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | keeping with these findings systemic administration of ibuprofen a non-selective COX inhibitor caused deficits in spatial learning in the water maze |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 0.3 | the increase in PGE 2 and brain-derived growth factor (BDNF) BDNF levels following LTP and spatial learning |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 0.3 | LTP and spatial learning most likely through an increase in BDNF levels supporting the hypothesis that COX activity plays a permissive |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | through an increase in BDNF levels supporting the hypothesis that COX activity plays a permissive role in synaptic plasticity and spatial |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF-associated | 0.3 | a permissive role in synaptic plasticity and spatial learning via BDNF-associated mechanisms ( 23 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2-inhibitor | 0.0 | not PGD 2 reversed the suppression of LTP induced by COX-2-inhibitor in hippocampal dentate granule neurons in vitro ( 24 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | 2 which is preferentially formed during the enzymatic activity of COX-2 rather than of COX-1 could participate to synaptic plasticity through |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | formed during the enzymatic activity of COX-2 rather than of COX-1 could participate to synaptic plasticity through several mechanisms including modulation |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | neocortical blood flow in response to vibrissal stimulation by the COX-2 inhibitor NS398 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2-derived | 0.0 | Moreover COX-2-derived PGs are involved in the coupling of synaptic plasticity with |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | hyperemic response was also impaired in mutant mice lacking of COX-2 ( 26 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | spite of the emerging evidence of a physiological role for COX-2 in brain development and function COX-2 knockout mice show no |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | a physiological role for COX-2 in brain development and function COX-2 knockout mice show no gross abnormalities of brain anatomy |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | In addition significant compensatory effects of COX-1 and possibly COX-3 cannot be ruled out |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-3 | 0.3 | In addition significant compensatory effects of COX-1 and possibly COX-3 cannot be ruled out |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | In this light the expression of COX-2 and its contribution to the pathogenic events in MS have |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | COX-2 immunoreactivity has been found in experimental autoimmune encephalomyelitis (EAE), EAE |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | proteolipid protein revealed that during the acute phase of EAE COX-2 expression is confined within infiltrating macrophages and ramified microglia close |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Very rare reactive astrocytes expressed COX-2 in this phase but their number significantly increased during relapse |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | but their number significantly increased during relapse phase suggesting that COX-2 induction in astrocytes could be due to soluble factors i.e |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | a peptide of another myelin protein the myelin basic protein COX-2 immunoreactivity was exclusively found associated with neurons and endothelial cells |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2-positive | 0.0 | The number of COX-2-positive endothelial cells increased with the progression of the disease most |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | Macrophage/ Macrophage microglia-like cells expressing COX-1 were disseminated throughout the brain parenchyma of control animals |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1-positive | 0.0 | In EAE the number of COX-1-positive macrophages increased along with that of COX-2-positive cells |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2-positive | 0.0 | the number of COX-1-positive macrophages increased along with that of COX-2-positive cells |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | brain parenchyma breakdown of BBB primary demyelination and axon damage COX-2 expression was restricted to major infiltrating hematogenous cell populations such |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | macrophages but the possibility that some endothelial cells also expressed COX-2 could not be ruled out |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Neuronal COX-2 was not affected by the ongoing inflammation |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | broad area surrounding the inflammatory lesions there was no obvious COX-2 staining in these cells indicating that the upregulation of COX-2 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | COX-2 staining in these cells indicating that the upregulation of COX-2 expression in this model of chronic immune-mediated lesions is remarkably |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | A similar restricted COX-2 expression has been described in brain tissues from 7 MS |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | these specimens characterized by the presence of chronic active lesions COX-2 expression was studied by sophisticated confocal microscopy analysis |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2-positive | 0.0 | COX-2-positive cells were present in all chronic active lesions examined and |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | COX-2 immunoreactivity was largely but not exclusively associated with cells expressing |
| 3613 | FCGR1A | Fc fragment of IgG, high affinity Ia, receptor (CD64) | CD64 | 1.0 | exclusively associated with cells expressing the macrophage/microglial macrophage microglial marker CD64 the FC receptor typically associated with activated macrophages |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | However not all CD64-positive cells expressed COX-2 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Expression of COX-2 was frequently associated with that of inducible NO synthase (iNOS), |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 1.0 | was frequently associated with that of inducible NO synthase (iNOS), iNOS suggesting that both enzymes could contribute to the progression of |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | The authors also propose that the colocalization of COX-2 and iNOS may be functionally linked to oligodendroglial excitotoxic death |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 1.0 | The authors also propose that the colocalization of COX-2 and iNOS may be functionally linked to oligodendroglial excitotoxic death in MS |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Nonetheless a protective role of COX-2 in MS cannot be excluded |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-derived | 0.0 | co-administration of misoprostol a PGE 2 analog suggesting that distinct COX-derived products (i.e i.e ROS and PGs may have protective or |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | gene encoding for the Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 account for a familial form of ALS linked to chromosome |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | has led to the development of transgenic mice expressing mutant SOD1 with phenotype that mimics clinical and pathological characteristics of the |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | The well-established role of COX-2 in inflammation and in glutamate-dependent neurotoxicity has set the basis |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | glutamate-dependent neurotoxicity has set the basis for the hypothesis of COX-2 involvement in ALS pathogenesis |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | COX-2 mRNA and protein were increased in postmortem spinal cords of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | spinal cords of ALS patients ( 42 and transgenic mutated SOD1 mice ( 43 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | of PGE 2 tissue levels paralleled the increased expression of COX-2 ( 43 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | The cell types expressing COX-2 have been identified in both animal and human specimens |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Under normal conditions COX-2 is expressed in neurons in the spinal cord dorsal and |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | In postmortem spinal cord of ALS patients COX-2 expression was markedly increased and localized to both neurons and |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2-positive | 0.0 | The number of COX-2-positive motor neurons and interneurons was significantly increased in spite of |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | In addition COX-2 was associated with astrocytes and and to a much lesser |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | In contrast COX-1 immunoreactivity was confined to some microglial cells and there was |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | A similar pattern of COX-2 expression was reported for the mutated SOD1 transgenic mice ( |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | similar pattern of COX-2 expression was reported for the mutated SOD1 transgenic mice ( 43 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | The role of COX-2 activity in ALS was examined by using selective COX-2 inhibitors |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | of COX-2 activity in ALS was examined by using selective COX-2 inhibitors |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | In the first study the COX-2 inhibitor SC236 significantly protected motor neurons in an organotypic spinal |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | These findings suggested that COX-2 could take part in the excitotoxic damage caused by elevated |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | Subsequently the same group showed that treatment of SOD1 transgenic mice with COX-2 inhibitor celecoxib significantly delayed the onset |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | same group showed that treatment of SOD1 transgenic mice with COX-2 inhibitor celecoxib significantly delayed the onset of disease prolonged the |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | These studies suggest that inhibition of COX-2 could have therapeutic benefits by altering the cascade of events |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | However in these studies mice received the COX-2 inhibitor treatment beginning several weeks before the onset of disease |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Thus the efficacy of COX-2 inhibition in the presence of overt clinical signs of disease |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Several mechanisms could be triggered by COX-2 overexpression |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | to the enhancing effect of PGE 2 on glutamate release COX-2 could contribute to oxidative stress-mediated damage by producing oxidizing reactive |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.4 | In transgenic mutated SOD1 mice COX-2 and iNOS are induced with a similar temporal |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | In transgenic mutated SOD1 mice COX-2 and iNOS are induced with a similar temporal pattern and |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 1.0 | In transgenic mutated SOD1 mice COX-2 and iNOS are induced with a similar temporal pattern and co-expression of |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | COX-2 could also contribute to ALS by promoting inflammatory processes |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | been related to free radical scavenging effects rather then to COX inhibition or attenuation of inflammation ( 51 52 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | Two studies have investigated the expression of COX isoforms in postmortem PD specimens or in PD experimental models |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | The first study reported an increased expression of COX-2 in ameboid or activated microglial cells in the substantia nigra |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | nigra from 11 idiopathic PD patients whereas neuronal and astroglial COX-2 expression was not different in the control and PD groups |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | Moderate COX-1 immunoreactivity was observed in some neuronal somata and processes and |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | that the greater potential for PG synthesis is associated to COX-2 and microglial cells ( 53 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | the second and more recent study ( 52 showed that COX-2 is specifically induced in substantia nigra dopaminergic neurons in postmortem |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | The involvement of COX-2 in PD neurodegeneration was further suggested by the observation that |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | suggested by the observation that MPTP neurodegeneration was mitigated in COX-2 but not in COX-1 knock out mice |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | that MPTP neurodegeneration was mitigated in COX-2 but not in COX-1 knock out mice |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | The characteristic neuropathological signs of the disease are amyloid deposition of the proteinase-resistant prion protein (PrP PrP res or |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.3 | disease are amyloid deposition of the proteinase-resistant prion protein (PrP PrP res or PrP Sc astrocytosis and spongiform degeneration |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.3 | deposition of the proteinase-resistant prion protein (PrP PrP res or PrP Sc astrocytosis and spongiform degeneration |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.0 | of the prominent microglial activation classical pro-inflammatory mediators such as IL-1 IL-6 TNF- alpha and IFN- gamma were not detected in |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.0 | the prominent microglial activation classical pro-inflammatory mediators such as IL-1 IL-6 TNF- alpha and IFN- gamma were not detected in significant |
| 5438 | IFNG | interferon, gamma | IFN- | 0.3 | classical pro-inflammatory mediators such as IL-1 IL-6 TNF- alpha and IFN- gamma were not detected in significant amount in a murine |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF- | 0.4 | prominent microglial activation classical pro-inflammatory mediators such as IL-1 IL-6 TNF- alpha and IFN- gamma were not detected in significant amount |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | PGE 2 levels was associated with a strong induction of COX-2 expression which increased with the progression of disease and was |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1-positive | 0.0 | Few scattered COX-1-positive microglia-like cells were found in control and infected brains ( |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | sporadic CJD ( 57 suggesting that the selective upregulation of COX-2 in microglial cells is not characteristic of a specific prion |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | results were reported in a recent study in which both COX-1 and COX-2 were increased in sporadic CJD cortex ( 58 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | results were reported in a recent study in which both COX-1 and COX-2 were increased in sporadic CJD cortex ( 58 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | reported in a recent study in which both COX-1 and COX-2 were increased in sporadic CJD cortex ( 58 |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | COX-1 immunoreactivity was present in macrophages/microglial macrophages microglial cells whereas COX-2 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | COX-1 immunoreactivity was present in macrophages/microglial macrophages microglial cells whereas COX-2 was predominantly in neurons mRNAs and proteins of both isoforms |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | Increased COX activity in prion diseases was confirmed by 2 studies ( |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | the CSF of CJD patients and the high expression of COX-2 in microglial cells in experimental prion diseases suggest that PGE |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | cells with apoptotic neurons has been reported to selectively promote COX-2 expression and PGE 2 synthesis ( 61 |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.3 | death as suggested by the observation that in neuroblastoma cells PrP peptides increase PGE 2 levels and COX-1 inhibitors protect against |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | in neuroblastoma cells PrP peptides increase PGE 2 levels and COX-1 inhibitors protect against PrP toxicity ( 62 |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.3 | peptides increase PGE 2 levels and COX-1 inhibitors protect against PrP toxicity ( 62 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | By contrast the non-selective COX inhibitor indomethacin had no significant effect on onset of clinical |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | in the elderly characterized by senile plaques neurofibrillary tangles and amyloid angiopathy |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX | 0.6 | The concept of a pathogenic role of COX in AD is deeply rooted in epidemiological studies reporting an |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | Over the last 10 years several analyses of COX-1 and COX-2 expressions have been carried out in animal models |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Over the last 10 years several analyses of COX-1 and COX-2 expressions have been carried out in animal models |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Over the last 10 years several analyses of COX-1 and COX-2 expressions have been carried out in animal models and postmortem |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | still controversial body of evidence pointing to the involvement of COX-2 in the cascade of events leading to neurodegeneration in AD |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | COX-2 mRNA levels in AD brains were reported as either decreased |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | 9 65 66 possibly because of the short half-life of COX-2 transcripts or individual variability of inflammatory-related processes ( 67 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Several studies reported increased neuronal COX-2 immunoreactivity compared to control brain tissues ( 9 68 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | However in other studies in which COX-2 expression was related to specific hallmarks of the disease such |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2-positive | 0.0 | dementia rating and Braak stage of disease the number of COX-2-positive neurons decreased with the severity of dementia |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2-positive | 0.0 | In end stage AD COX-2-positive neurons were significantly fewer than in non-demented controls ( 68 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | more recent study ( 70 the number of neurons expressing COX-2 negatively correlated with the Braak score for amyloid deposits although |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | neurons expressing COX-2 negatively correlated with the Braak score for amyloid deposits although a moderate albeit non-significant COX-2 increase was found |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Braak score for amyloid deposits although a moderate albeit non-significant COX-2 increase was found at Braak stage A corresponding to the |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | COX-2 immunoreactivity did not correlate with Braak staging for neurofibrillary changes |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | These recent studies suggest that COX-2 expression varies with the disease stage and this may explain |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | also reported a colocalization and a significant correlation of neuronal COX-2 expression with cell cycle regulators involved in controlling the G |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Although there are some indications that COX-2 might regulate cell cycle progression ( 70 the functional link |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | regulate cell cycle progression ( 70 the functional link between COX-2 and cell cycle alteration remains elusive |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Nonetheless it can be suggested that COX-2 and cell cycle proteins are involved in early steps leading |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | In contrast to COX-2 the levels of COX-1 mRNA and protein were not significantly |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | In contrast to COX-2 the levels of COX-1 mRNA and protein were not significantly altered in AD brains |
| 9604 | PTGS1 | prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase) | COX-1 | 2.3 | COX-1 appeared to be mainly expressed by microglial cells found in |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | be mainly expressed by microglial cells found in association with amyloid deposits regardless their ramified or activated morphology ( 71 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2-positive | 0.0 | is consistent with the slight increase in the number of COX-2-positive neurons at Braak stage A as well as with the |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2-positive | 0.0 | Braak stage A as well as with the reduction in COX-2-positive neurons reported in patients with severe dementia and Braak end-stage |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | The moderate increase in COX-2 expression and activity at very early stages of AD could |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Upregulation of neuronal COX-2 is associated with ischemia and excitotoxicity suggesting that COX-2 is |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | neuronal COX-2 is associated with ischemia and excitotoxicity suggesting that COX-2 is involved in neurotoxic mechanisms |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Increased susceptibility to excitotoxicity in COX-2 over-expressing neurons and neuroprotection by COX-2 inhibition has been shown |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | susceptibility to excitotoxicity in COX-2 over-expressing neurons and neuroprotection by COX-2 inhibition has been shown in several experimental models ( 64 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Nonetheless increased COX-2 expression could be an adaptive reaction to pathological events such |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Taking into account the positive and negative effects of increased COX-2 activity and the emerging role of COX-2-derived PGs in brain |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | is difficult to predict the final outcome of long-term therapeutic COX-2 inhibition |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2-derived | 0.0 | effects of increased COX-2 activity and the emerging role of COX-2-derived PGs in brain function it is difficult to predict the |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | At present clinical trials of selective COX-2 inhibitors have not been as convincing as expected but these |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | the peroxisome proliferator-activated receptor- gamma suggesting that selective inhibition of COX-2 may not be the optimal therapeutic strategy ( 64 |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Since its discovery in early 1990s COX-2 has emerged as a major player in inflammatory reactions in |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Evidence from several laboratories indicates that COX-2 is induced in various inflammatory settings is the main source |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | By extension COX-2 expression in brain has been associated with pro-inflammatory activities thought |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | should be borne in mind when considering the significance of COX-2 activity in brain diseases |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | First COX-2 is expressed under normal conditions and contributes to fundamental brain |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | the last decade the evidence of a direct role of COX-2 in neurodegenerative events is still controversial and further experimental and |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | are required to improve our knowledge of how and when COX-2 inhibition may have beneficial effects for patients suffering from inflammatory |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | neurons glia endothelial cells and infiltrating blood cells can express COX-2 in brain |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Over-expression of COX-2 in each of these cells may have different functional consequences |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | outcome is likely to depend on the prevailing product of COX-2 activity including PGs with different functions and free radicals |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | particularly susceptible to damage caused by free radicals generated through COX-2 peroxidase activity whereas glial cells are more resistant |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | Specific signals seem responsible for COX-2 induction and/or and or over-expression in particular cell types such |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | The beneficial effects of specific and non-specific COX-2 inhibitors in several experimental models and epidemiological studies are an |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-2 | 4.4 | studies are an indirect proof of the causative role of COX-2 in neurodegeneration as COX-independent mechanisms cannot be excluded |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | COX-independent | 0.0 | proof of the causative role of COX-2 in neurodegeneration as COX-independent mechanisms cannot be excluded |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 is the inducible isoform rapidly expressed in several cell types in response to growth factors cytokines and pro inflammatory molecules. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | since its discovery in the early 1990s cox 2 has emerged as a major player in inflammatory reactions in peripheral tissues. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | by extension cox 2 expression in brain has been associated with pro inflammatory activities thought to be instrumental in neurodegenerative processes of several acute and chronic diseases. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | first in the central nervous system cox 2 is expressed under normal conditions and contributes to fundamental brain functions such as synaptic activity memory consolidation and functional hyperemia. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in spite of the intense research of the last decade the evidence of a direct role of cox 2 in neurodegenerative events is still controversial. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | furthermore the emerging role of cox 2 in behavioral and cognitive functions will be discussed. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | besides a constitutive isoform cox 1 which is widely distributed in virtually all cell types and is thought to mediate physiological responses a second and inducible isoform termed cox 2 was identified in the early 1990s 4 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 is rapidly expressed in several cell types in response to growth factors cytokines and pro inflammatory molecules and has emerged as the isoform primarily responsible for prostanoid production in acu |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 1 and cox 2 are coded by 2 distinct genes located on human chromosome 9 and 1 respectively. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the cox 2 gene is characterized by the presence of a tata box and a multitude of binding sites for transcription factors in its promoter region which account for the complex regulation of cox 2 expression. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | n a long 3' untranslated region which has been found in many immediate early genes acts as mrna instability determinant or as translation inhibitory element suggesting post transcriptional control of cox 2 expression. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | ites are conserved a few crucial substitutions cause important conformational variations in the active site pocket of the 2 isoenzymes which could account for the different sensitivities of cox 1 and cox 2 to specific inhibitors 5 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | one important difference between the 2 isoforms is the 18 amino acid insert near the cox 2 c terminus which is not present in cox 1 and has allowed the production of specific antibodies. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | however in brain testes and kidney macula densa cells both cox 1 and cox 2 are expressed under physiological conditions 2 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in rat brain cox 1 and cox 2 immunoreactivities are present in discrete neuronal populations distributed in distinct areas of cerebral cortex and hippocampus. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | similarly mrnas for both cox 1 and cox 2 are present in several regions of human brain although cox 2 is the prominent isoform particularly in the hippocampus 8 9 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the relative contribution of cox 1 and cox 2 activity to brain pathology and physiology has been recently questioned 10 11 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | on one side it has been argued that cox 1 activity in brain diseases has been overlooked; on the other side mandatory evidence suggests that cox 2 plays a special role in normal neuronal function and in neurotoxicity. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | although this debate will be solved only by further clinical and experimental studies it is clear that the popular paradigm by which cox 1 serves physiological functions and cox 2 is responsible for _amp_#147;pathological_amp_#148; pgs cannot explain an increasing number of findings. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | over expression of cox 2 has been associated with neurotoxicity in acute conditions such as hypoxia/ ischemia and seizures. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | however the beneficial or detrimental role played by cox 2 in inflammatory and neurodegenerative brain pathologies is still controversial. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | first the emerging role of cox 2 in cognitive functions will be discussed since understanding the role of cox 2 in brain function is an important prerequisite to fully understanding how to exploit the potential benefits of cox 2 inhibition in disabling neurological diseases. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in brain function is an important prerequisite to fully understanding how to exploit the potential benefits of cox 2 inhibition in disabling neurological diseases. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in mammalian brain cox 2 is constitutively expressed in specific neuronal populations under normal physiological conditions. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in rat brain cox 2 mrna and immunoreactivity were detected in dentate gyrus granule cells pyramidal cell neurons in the hippocampus the piriform cortex superficial cell layers of neocortex the amygdala and at low level |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | this _amp_#147;constitutive_amp_#148; neuronal cox 2 expression should be more correctly regarded as _amp_#147;dynamically_amp_#148; regulated since it is dependent on normal synaptic activity is rapidly increased during seizures or ischemia and is dow |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the dependence of cox 2 expression on natural excitatory synaptic activity is supported by the presence of cox 2 immunoreactivity in distal dendrites and dendritic spines which are involved in synaptic signaling and by its exclusive localization to excitatory glutamatergic neurons. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | furthermore the heterogeneous distribution within a neuronal population is compatible with induction of cox 2 in subsets of neurons in response to natural excitatory synaptic stimulation as shown for other immediate early genes activated by excitatory stimulation 14 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the involvement of cox 2 in synaptic activity is further supported by the developmental profile of cox 2 expression. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in rat brain cox 2 expression follows developmental gradients and coincides with the critical period of activity dependent cortical development 17 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | yndrome_amp_#151;a neurological disorder associated with mental retardation defective development of cortical neurons and abnormalities of dendritic branching_amp_#151;the laminar pattern of cortical cox 2 immunoreactivity is disrupted in that cox 2 positive neurons are decreased in number and randomly distributed 18 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | immunoreactivity is disrupted in that cox 2 positive neurons are decreased in number and randomly distributed 18 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | rats subjected to selective destruction of basal forebrain cholinergic neurons during the first post natal week showed decreased levels of cox 2 but not cox 1 in the hippocampus at adulthood. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | this effect was accompanied by impairment in social memory suggesting that the early loss of hippocampal cholinergic input may impact on the expression of cox 2 in hippocampal neurons and on the functional role of pgs in synaptic activity 19 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | indirect evidence of cox 2 involvement in synaptic plasticity has been obtained in the recent years by using cox inhibitors in in vivo and in vitro models of synaptic plasticity. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 inhibitors but not cox 1 selective inhibitors administered systemically shortly after training in the morris water maze a hippocampal dependent learning task have been shown to impair spatial memory |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in addition pre training infusion of a cox 2 specific inhibitor celecoxib in the hippocampus of adult rats impaired acquisition of the morris water maze suggesting that in rats cox 2 activity in the hippocampus is necessary for both memory and learning of a spatial task 22 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in agreement with this hypothesis pge 2 but not pgd 2 reversed the suppression of ltp induced by cox 2 inhibitor in hippocampal dentate granule neurons in vitro 24 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | pge 2 which is preferentially formed during the enzymatic activity of cox 2 rather than of cox 1 could participate to synaptic plasticity through several mechanisms including modulation of adrenergic noradrenergic and glutamatergic neurotransmission remodeling of actin in th |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | moreover cox 2 derived pgs are involved in the coupling of synaptic plasticity with cerebral blood flow as suggested by the attenuation of the increase in neocortical blood flow in response to vibrissal stimulation |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | pgs are involved in the coupling of synaptic plasticity with cerebral blood flow as suggested by the attenuation of the increase in neocortical blood flow in response to vibrissal stimulation by the cox 2 inhibitor ns398. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the hyperemic response was also impaired in mutant mice lacking of cox 2 26 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in spite of the emerging evidence of a physiological role for cox 2 in brain development and function cox 2 knockout mice show no gross abnormalities of brain anatomy. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in this light the expression of cox 2 and its contribution to the pathogenic events in ms have been explored in several animal models and in ms patients. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 immunoreactivity has been found in experimental autoimmune encephalomyelitis eae an extensively used animal model. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | analysis of spinal cord of sjl mice immunized with a peptide of the myelin constituent proteolipid protein revealed that during the acute phase of eae cox 2 expression is confined within infiltrating macrophages and ramified microglia close to the inflammatory infiltrates. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | very rare reactive astrocytes expressed cox 2 in this phase but their number significantly increased during relapse phase suggesting that cox 2 induction in astrocytes could be due to soluble factors i.e. cytokines produced during the protracted inflammatory insults 30 . |
| 6925 | MBP | myelin basic protein | myelin basic protein | 1.0 | in a different eae model in which lewis rats were immunized with a peptide of another myelin protein the myelin basic protein cox 2 immunoreactivity was exclusively found associated with neurons and endothelial cells 31 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in a different eae model in which lewis rats were immunized with a peptide of another myelin protein the myelin basic protein cox 2 immunoreactivity was exclusively found associated with neurons and endothelial cells 31 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the number of cox 2 positive endothelial cells increased with the progression of the disease most prominently in areas of cellular infiltration. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in eae the number of cox 1 positive macrophages increased along with that of cox 2 positive cells. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | sensitivity response to heat killed bacillus calmette gu_amp_#233;rin which results in t cell and macrophage recruitment to the brain parenchyma breakdown of bbb primary demyelination and axon damage cox 2 expression was restricted to major infiltrating hematogenous cell populations such as neutrophils and mononuclear phagocytes and to perivascular cells of the blood vessels in the vicinity of the lesi |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | these perivascular cells were identified as macrophages but the possibility that some endothelial cells also expressed cox 2 could not be ruled out. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | neuronal cox 2 was not affected by the ongoing inflammation. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in spite of the extensive astrocyte and microglial reaction occurring over a broad area surrounding the inflammatory lesions there was no obvious cox 2 staining in these cells indicating that the upregulation of cox 2 expression in this model of chronic immune mediated lesions is remarkably restricted to the lesion sites 32 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | staining in these cells indicating that the upregulation of cox 2 expression in this model of chronic immune mediated lesions is remarkably restricted to the lesion sites 32 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | a similar restricted cox 2 expression has been described in brain tissues from 7 ms patients 33 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in these specimens characterized by the presence of chronic active lesions cox 2 expression was studied by sophisticated confocal microscopy analysis. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 positive cells were present in all chronic active lesions examined and generally located on the border of myelinated regions. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 immunoreactivity was largely but not exclusively associated with cells expressing the macrophage/microglial marker cd64 the fc receptor typically associated with activated macrophages. |
| 24692 | FCAMR | Fc receptor, IgA, IgM, high affinity | fc receptor | 1.0 | cox 2 immunoreactivity was largely but not exclusively associated with cells expressing the macrophage/microglial marker cd64 the fc receptor typically associated with activated macrophages. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | however not all cd64 positive cells expressed cox 2. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | expression of cox 2 was frequently associated with that of inducible no synthase inos suggesting that both enzymes could contribute to the progression of ms through their ability to produce free radicals such as superox |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the authors also propose that the colocalization of cox 2 and inos may be functionally linked to oligodendroglial excitotoxic death in ms. indeed both pge 2 and peroxinitrite could increase the local concentration of glutamate to toxic levels by inducing ca |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | nonetheless a protective role of cox 2 in ms cannot be excluded. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the well established role of cox 2 in inflammation and in glutamate dependent neurotoxicity has set the basis for the hypothesis of cox 2 involvement in als pathogenesis. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 mrna and protein were increased in postmortem spinal cords of als patients 42 and transgenic mutated sod1 mice 43 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | elevation of pge 2 tissue levels paralleled the increased expression of cox 2 43 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the cell types expressing cox 2 have been identified in both animal and human specimens. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | under normal conditions cox 2 is expressed in neurons in the spinal cord dorsal and ventral horns as well as in dorsal root ganglia. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in postmortem spinal cord of als patients cox 2 expression was markedly increased and localized to both neurons and glial cells. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the number of cox 2 positive motor neurons and interneurons was significantly increased in spite of the expected overall reduction in the total number of neurons. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in addition cox 2 was associated with astrocytes and and to a much lesser extent with microglial cells. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | a similar pattern of cox 2 expression was reported for the mutated sod1 transgenic mice 43 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the role of cox 2 activity in als was examined by using selective cox 2 inhibitors. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in the first study the cox 2 inhibitor sc236 significantly protected motor neurons in an organotypic spinal cord culture model in which neuronal death is induced by treo hydroaspartate an inhibitor of astrocytic glutamate re upt |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | these findings suggested that cox 2 could take part in the excitotoxic damage caused by elevated glutamate levels. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | subsequently the same group showed that treatment of sod1 transgenic mice with cox 2 inhibitor celecoxib significantly delayed the onset of disease prolonged the survival and reduced the spinal neurodegeneration and glial activation 47 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | these studies suggest that inhibition of cox 2 could have therapeutic benefits by altering the cascade of events leading to the progressive neuronal death in als patients. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | however in these studies mice received the cox 2 inhibitor treatment beginning several weeks before the onset of disease defined as a 30_amp_#37; decrease in motor performance. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | thus the efficacy of cox 2 inhibition in the presence of overt clinical signs of disease remains to be investigated. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | several mechanisms could be triggered by cox 2 overexpression. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in addition to the enhancing effect of pge 2 on glutamate release cox 2 could contribute to oxidative stress mediated damage by producing oxidizing reactive species during the peroxidase activity fig 1 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in transgenic mutated sod1 mice cox 2 and inos are induced with a similar temporal pattern and co expression of the 2 enzymes as discussed in the previous section could lead to the formation of more reactive free radical species such as |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 could also contribute to als by promoting inflammatory processes. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the first study reported an increased expression of cox 2 in ameboid or activated microglial cells in the substantia nigra from 11 idiopathic pd patients whereas neuronal and astroglial cox 2 expression was not different in the control and pd groups. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | moderate cox 1 immunoreactivity was observed in some neuronal somata and processes and in few glial cells in both groups suggesting that the greater potential for pg synthesis is associated to cox 2 and microglial cells 53 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | by contrast the second and more recent study 52 showed that cox 2 is specifically induced in substantia nigra dopaminergic neurons in postmortem pd specimens and in the 1 methyl 4 phenyl 1 2 3 6 tetrahydropyridine mptp mouse model. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the involvement of cox 2 in pd neurodegeneration was further suggested by the observation that mptp neurodegeneration was mitigated in cox 2 but not in cox 1 knock out mice. |
| 9449 | PRNP | prion protein (p27-30) (Creutzfeldt-Jakob disease, Gerstmann-Strausler-Scheinker syndrome, fatal familial insomnia) | prion protein prp | 1.0 | the characteristic neuropathological signs of the disease are amyloid deposition of the proteinase resistant prion protein prp res or prp sc astrocytosis and spongiform degeneration. |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | in spite of the prominent microglial activation classical pro inflammatory mediators such as il 1 il 6 tnf [alpha] and ifn [gamma] were not detected in significant amount in a murine model of prion disease in which c57bl/6j mice are infected with scrapie the prion form affecting sheep. |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | in spite of the prominent microglial activation classical pro inflammatory mediators such as il 1 il 6 tnf [alpha] and ifn [gamma] were not detected in significant amount in a murine model of prion disease in which c57bl/6j mice are infected with scrapie the prion form affecting sheep. |
| 11765 | TGFA | transforming growth factor, alpha | transforming growth factor | 1.0 | by contrast the immunoregulatory cytokine transforming growth factor [beta] and pge 2 were increased 54 55 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the increase in hippocampal pge 2 levels was associated with a strong induction of cox 2 expression which increased with the progression of disease and was specifically localized to microglial cells 56 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | were then confirmed in a second murine model in which ch3 mice were infected with homogenates from 2 cases of genetic cjd and 3 cases of sporadic cjd 57 suggesting that the selective upregulation of cox 2 in microglial cells is not characteristic of a specific prion agent or mouse strain. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | different results were reported in a recent study in which both cox 1 and cox 2 were increased in sporadic cjd cortex 58 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 1 immunoreactivity was present in macrophages/microglial cells whereas cox 2 was predominantly in neurons. mrnas and proteins of both isoforms were higher in tissue from temporal lobe of 1 cjd patient when compared to 1 neuropathologically unaltered control case. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the increased levels of pge 2 in the csf of cjd patients and the high expression of cox 2 in microglial cells in experimental prion diseases suggest that pge 2 synthesis may be associated with the clearance of apoptotic neurons. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in cjd abundance of apoptotic neurons correlated well with microglial activation 60 and recently interaction of microglial cells with apoptotic neurons has been reported to selectively promote cox 2 expression and pge 2 synthesis 61 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | over the last 10 years several analyses of cox 1 and cox 2 expressions have been carried out in animal models and postmortem ad brain tissues providing a substantial but still controversial body of evidence pointing to the involvement of cox 2 in the cascade |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | expressions have been carried out in animal models and postmortem ad brain tissues providing a substantial but still controversial body of evidence pointing to the involvement of cox 2 in the cascade of events leading to neurodegeneration in ad. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 mrna levels in ad brains were reported as either decreased or increased 9 65 66 possibly because of the short half life of cox 2 transcripts or individual variability of inflammatory related processes 67 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | several studies reported increased neuronal cox 2 immunoreactivity compared to control brain tissues 9 68 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | however in other studies in which cox 2 expression was related to specific hallmarks of the disease such as clinical dementia rating and braak stage of disease the number of cox 2 positive neurons decreased with the severity of dementia. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in end stage ad cox 2 positive neurons were significantly fewer than in non demented controls 68 69 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in a more recent study 70 the number of neurons expressing cox 2 negatively correlated with the braak score for amyloid deposits although a moderate albeit non significant cox 2 increase was found at braak stage a corresponding to the mildest stage of disease when compared to non demented control cases. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | cox 2 immunoreactivity did not correlate with braak staging for neurofibrillary changes. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | these recent studies suggest that cox 2 expression varies with the disease stage and this may explain the controversial findings reported in the literature. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | hoozemans et al also reported a colocalization and a significant correlation of neuronal cox 2 expression with cell cycle regulators involved in controlling the g 0 / g 1 phase such as cyclin d1 and e and the retinoblastoma protein 69 70 . |
| 1582 | CCND1 | cyclin D1 | cyclin d1 | 1.0 | hoozemans et al also reported a colocalization and a significant correlation of neuronal cox 2 expression with cell cycle regulators involved in controlling the g 0 / g 1 phase such as cyclin d1 and e and the retinoblastoma protein 69 70 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | although there are some indications that cox 2 might regulate cell cycle progression 70 the functional link between cox 2 and cell cycle alteration remains elusive. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | nonetheless it can be suggested that cox 2 and cell cycle proteins are involved in early steps leading to neurodegeneration. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in contrast to cox 2 the levels of cox 1 mrna and protein were not significantly altered in ad brains 9 72 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | this pattern is consistent with the slight increase in the number of cox 2 positive neurons at braak stage a as well as with the reduction in cox 2 positive neurons reported in patients with severe dementia and braak end stage disease as previously reported 68 70 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the moderate increase in cox 2 expression and activity at very early stages of ad could explain the primary protective of nsaids by preventing early steps leading to neurodegeneration. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | upregulation of neuronal cox 2 is associated with ischemia and excitotoxicity suggesting that cox 2 is involved in neurotoxic mechanisms. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | increased susceptibility to excitotoxicity in cox 2 over expressing neurons and neuroprotection by cox 2 inhibition has been shown in several experimental models 64 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | nonetheless increased cox 2 expression could be an adaptive reaction to pathological events such as cerebrovascular dysfunction early inflammatory processes or oxidative stress in the attempt to restore lost physiological funct |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | taking into account the positive and negative effects of increased cox 2 activity and the emerging role of cox 2 derived pgs in brain function it is difficult to predict the final outcome of long term therapeutic cox 2 inhibition. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | derived pgs in brain function it is difficult to predict the final outcome of long term therapeutic cox 2 inhibition. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | at present clinical trials of selective cox 2 inhibitors have not been as convincing as expected but these failures may be related to drug selection and dose duration of treatment and state of disease of selected patients 64 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | echanisms such as lowering of a[beta] peptide levels reduction in the plaque pathology and activation of the peroxisome proliferator activated receptor [gamma] suggesting that selective inhibition of cox 2 may not be the optimal therapeutic strategy 64 . |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | since its discovery in early 1990s cox 2 has emerged as a major player in inflammatory reactions in peripheral tissues. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | evidence from several laboratories indicates that cox 2 is induced in various inflammatory settings is the main source of pgs responsible for clinical signs of inflammation and its inhibition leads to anti inflammatory effects. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | by extension cox 2 expression in brain has been associated with pro inflammatory activities thought to be instrumental in neurodegenerative processes of several acute and chronic diseases. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | however 2 major aspects should be borne in mind when considering the significance of cox 2 activity in brain diseases. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | first cox 2 is expressed under normal conditions and contributes to fundamental brain functions such as synaptic activity memory consolidation and functional hyperemia. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in spite of the intense research of the last decade the evidence of a direct role of cox 2 in neurodegenerative events is still controversial and further experimental and clinical studies are required to improve our knowledge of how and when cox 2 inhibition may have beneficial effects for |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | in neurodegenerative events is still controversial and further experimental and clinical studies are required to improve our knowledge of how and when cox 2 inhibition may have beneficial effects for patients suffering from inflammatory and degenerative neuropathologies. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | several cell types including resident cells i.e neurons glia endothelial cells and infiltrating blood cells can express cox 2 in brain. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | over expression of cox 2 in each of these cells may have different functional consequences and its final outcome is likely to depend on the prevailing product of cox 2 activity including pgs with different functions and free radicals. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | neurons are particularly susceptible to damage caused by free radicals generated through cox 2 peroxidase activity whereas glial cells are more resistant. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | specific signals seem responsible for cox 2 induction and/or over expression in particular cell types such as glutamate in neurons cytokines in astrocytes and apoptotic neurons in microglia. |
| 9605 | PTGS2 | prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | cox 2 | 1.0 | the beneficial effects of specific and non specific cox 2 inhibitors in several experimental models and epidemiological studies are an indirect proof of the causative role of cox 2 in neurodegeneration as cox independent mechanisms cannot be excluded. |