CIDeRplusGeneral Information:
| Id: | 310 |
| Diseases: |
Amyotrophic lateral sclerosis
|
| Mus musculus | |
| SOD1 wt or SOD1G93A or SOD1G85R transgenic mouse, transfected with human wt SOD1 or human SOD1G93A or human SOD1G85R | |
| BTO:0000312 motoneuron | |
| article | |
| Reference: | Raoul C et al.(2006) Chronic activation in presymptomatic amyotrophic lateral sclerosis (ALS) mice of a feedback loop involving Fas, Daxx, and FasL Proc. Natl. Acad. Sci. U.S.A. 103: 6007-6012 [PMID: 16581901] |
Interaction Information:
| Comment | In both control and mutant SOD1 motoneurons, exogenous NO (addition of Detanonoate) leads to up-regulation of FasL. As a reporter of Fas activation, phophorylation of p38 kinase was quantified. However, only in the presence of G93A or G85R mutant forms of SOD1 does this mechanism lead to a Fas-dependent increase in phosphorylation of p38 kinase. |
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Formal Description Interaction-ID: 1224 |
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| Comment | Levels of Fas were similar between C57BL/6 and mutant SOD1 motoneurons and unchanged by the presence of NO donors such as Detanonoate. |
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Formal Description Interaction-ID: 1228 |
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| Drugbank entries | Show/Hide entries for FAS |
| Comment | FasL expressed after NO exposure is mostly membrane-bound. |
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Formal Description Interaction-ID: 1230 |
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| Comment | NO leads to death of mutant, but not control, motoneurons. |
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Formal Description Interaction-ID: 1232 |
drug/chemical compound increases_activity of process |
| Comment | In mutant SOD1G93A and SOD1G85R, but not in control motoneurons, the upregulation of FasL results in activation of Fas, leading through Daxx to phosphorylation of p38 and further NO synthesis. This Fas/NO feedback amplification loop is required for motoneuron death in vitro. |
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Formal Description Interaction-ID: 1360 |
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| Drugbank entries | Show/Hide entries for FAS |
| Comment | In mutant SOD1G93A and SOD1G85R, but not in control motoneurons, the upregulation of FasL results in activation of Fas, leading through Daxx to phosphorylation of p38 and further NO synthesis. This Fas/NO feedback amplification loop is required for motoneuron death in vitro. |
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Formal Description Interaction-ID: 1364 |
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| Drugbank entries | Show/Hide entries for FAS |
| Comment | In mutant SOD1G93A and SOD1G85R, but not in control motoneurons, the upregulation of FasL results in activation of Fas, leading through Daxx to phosphorylation of p38 and further NO synthesis. This Fas/NO feedback amplification loop is required for motoneuron death in vitro. |
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Formal Description Interaction-ID: 1367 |
gene/protein increases_activity of gene/protein p38 MAPK |
| Comment | In both control and mutant SOD1 motoneurons, exogenous NO (addition of Detanonoate) leads to up-regulation of FasL. As a reporter of Fas activation, phophorylation of p38 kinase was quantified. However, only in the presence of G93A or G85R mutant forms of SOD1 does this mechanism lead to a Fas-dependent increase in phosphorylation of p38 kinase. |
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Formal Description Interaction-ID: 13452 |
|
| Comment | In both control and mutant SOD1 motoneurons, exogenous NO (addition of Detanonoate) leads to up-regulation of FasL. As a reporter of Fas activation, phophorylation of p38 kinase was quantified. However, only in the presence of G93A or G85R mutant forms of SOD1 does this mechanism lead to a Fas-dependent increase in phosphorylation of p38 kinase. |
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Formal Description Interaction-ID: 13454 |
|
| Comment | In both control and mutant SOD1 motoneurons, exogenous NO (addition of Detanonoate) leads to up-regulation of FasL. As a reporter of Fas activation, phophorylation of p38 kinase was quantified. However, only in the presence of G93A or G85R mutant forms of SOD1 does this mechanism lead to a Fas-dependent increase in phosphorylation of p38 kinase. |
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Formal Description Interaction-ID: 13456 |
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| Drugbank entries | Show/Hide entries for SOD1 |
| Comment | In mutant SOD1G93A and SOD1G85R, but not in control motoneurons, the upregulation of FasL results in activation of Fas, leading through Daxx to phosphorylation of p38 and further NO synthesis. This Fas/NO feedback amplification loop is required for motoneuron death in vitro. |
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Formal Description Interaction-ID: 13474 |
gene/protein increases_phosphorylation of gene/protein p38 MAPK |
| Comment | In mutant SOD1G93A and SOD1G85R, but not in control motoneurons, the upregulation of FasL results in activation of Fas, leading through Daxx to phosphorylation of p38 and further NO synthesis by upregulation of nNOS. This Fas/NO feedback amplification loop is required for motoneuron death in vitro. |
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Formal Description Interaction-ID: 13478 |
gene/protein p38 MAPK increases_quantity of gene/protein |
| Drugbank entries | Show/Hide entries for NOS1 |
| Comment | In mutant SOD1G93A and SOD1G85R, but not in control motoneurons, the upregulation of FasL results in activation of Fas, leading through Daxx to phosphorylation of p38 and further NO synthesis by upregulation of nNOS. This Fas/NO feedback amplification loop is required for motoneuron death in vitro. |
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Formal Description Interaction-ID: 13483 |
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| Drugbank entries | Show/Hide entries for NOS1 |