General Information:

Id: 350
Diseases: Amyotrophic lateral sclerosis
Mus musculus
BTO:0000312 motoneuron
article
Reference: Raoul C et al.(2002) Motoneuron death triggered by a specific pathway downstream of Fas. potentiation by ALS-linked SOD1 mutations. Neuron 35: 1067-1083 [PMID: 12354397]

Interaction Information:

Comment Neuronal NOS is specifically upregulated in motoneurons following Fas activation and its activity is essential for Fas-induced death. Fas activation in motoneurons leads to the transcription and translation of nNOS.
Formal Description
Interaction-ID: 1391

gene/protein

FAS

increases_expression of

gene/protein

NOS1

in Fas-activated motoneurons
Drugbank entries Show/Hide entries for FAS or NOS1
Comment Production of NO by nNOS is necessary for Fas to exert its killing effect in motoneurons.
Formal Description
Interaction-ID: 1397

drug/chemical compound

NO

increases_activity of

phenotype

motor neuron degeneration

in Fas-activated motoneurons
Comment Peroxynitrite was produced after Fas activation.
Formal Description
Interaction-ID: 1399

gene/protein

FAS

increases_quantity of

drug/chemical compound

Peroxynitrite

in Fas-activated motoneurons
Drugbank entries Show/Hide entries for FAS
Comment MAP kinase activation plays a role in Fas-induced death. There was an increase in relative levels of phospho-p38 following Fas activation but no change in the levels of phospho-JNK.
Formal Description
Interaction-ID: 1402

gene/protein

FAS

increases_activity of

gene/protein

MAPK14

in Fas-activated motoneurons
Drugbank entries Show/Hide entries for FAS or MAPK14
Comment MAP kinase activation plays a role in Fas-induced death. There was an increase in relative levels of phospho-p38 following Fas activation but no change in the levels of phospho-JNK.
Formal Description
Interaction-ID: 1411

gene/protein

FAS

NOT increases_activity of

gene/protein

MAPK8

in Fas-activated motoneurons
Drugbank entries Show/Hide entries for FAS or MAPK8
Comment MAP kinase activation plays a role in Fas-induced death. There was an increase in relative levels of phospho-p38 following Fas activation but no change in the levels of phospho-JNK.
Formal Description
Interaction-ID: 1413

gene/protein

FAS

NOT increases_activity of

gene/protein

MAPK9

in Fas-activated motoneurons
Drugbank entries Show/Hide entries for FAS or MAPK9
Comment p38 kinase controls nNOS transcription following Fas activation. Inhibiting p38 activity by SB203580 (a p38 inhibitor) strongly inhibited nNOS upregulation following Fas activation, so that one principal role of p38 in these conditions is to enhance NO production.
Formal Description
Interaction-ID: 1418

gene/protein

p38 MAPK

increases_expression of

gene/protein

NOS1

in Fas-activated motoneurons
Drugbank entries Show/Hide entries for NOS1
Comment ASK1 is required for Fas-induced motoneuron death.
Formal Description
Interaction-ID: 1423

gene/protein

MAP3K5

increases_activity of

phenotype

motor neuron degeneration

in Fas-activated motoneurons
Comment DAXX is involved in Fas-mediated motoneuron death. Overexpression of Daxx-DN (a dominant-negative form containing only the C-terminal Fas binding domain) saved motoneurons from Fas-triggered death. Daxx-DN completely prevented the Fas-induced increase in the number of nNOS-expressing cells.
Formal Description
Interaction-ID: 1424

gene/protein

DAXX

increases_activity of

phenotype

motor neuron degeneration

in Fas-activated motoneurons
Comment Mutant ASK1-K709R, a catalytically inactive enzyme, provided complete protection of motoneurons.
Formal Description
Interaction-ID: 1425

gene/protein mutant

MAP3K5-p.K709R

decreases_activity of

phenotype

motor neuron degeneration

in Fas-activated motoneurons
Comment Fas-triggered activation of caspase-8 in motoneurons is controlled by p38.
Formal Description
Interaction-ID: 1426

gene/protein

p38 MAPK

affects_activity of

gene/protein

CASP8

in Fas-activated motoneurons
Comment Fas activation triggers cytochrome c release from mitochondria.
Formal Description
Interaction-ID: 1427

gene/protein

FAS

increases_activity of

process

release of cytochrome c from mitochondria

in Fas-activated motoneurons
Drugbank entries Show/Hide entries for FAS
Comment The p38 kinase controls mitochondrial cytochrome c release. By treatment with the p38 inhibitor SB203580, the Fas-induced cytochrome c release was completely blocked. These observations suggest that p38 not only controls caspase-8 but also other downstream elements leading to cytochrome c release.
Formal Description
Interaction-ID: 1428

gene/protein

p38 MAPK

increases_activity of

process

release of cytochrome c from mitochondria

in Fas-activated motoneurons
Comment Production of NO by nNOS is necessary for Fas to exert its killing effect in motoneurons.
Formal Description
Interaction-ID: 2455

gene/protein

NOS1

increases_quantity of

drug/chemical compound

NO

in Fas-activated motoneurons
Drugbank entries Show/Hide entries for NOS1
Comment Neuronal NOS is specifically upregulated in motoneurons following Fas activation and its activity is essential for Fas-induced death. Fas activation in motoneurons leads to the transcription and translation of nNOS.
Formal Description
Interaction-ID: 13496

gene/protein

FAS

increases_quantity of

gene/protein

NOS1

in Fas-activated motoneurons
Drugbank entries Show/Hide entries for FAS or NOS1