Sildenafil treatment (Homo sapiens)

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Label legend4, 317, 23, 3413, 3514, 36191761911224, 30101211PDE4:NucleussGCPDE4AKT:PRKG1Nitric oxidePRKNZNF746Smooth musclerelaxationAMPAKT1PI3K CascadeAKT2TFAMGAPDH inhibitorsMitochondrialbiogenesisGTPNRF1GUCY1A2GAPDHGMPPDE5PDE4ANO-signalingcGMPPDE4DGSK3BPPARGC1AMAPKpathwaytideglusibsildenafilPDE4CNOS1PDE4BPDE4inhibitors825sGC:GUCY1B2GUCY1A1GUCY1B127, 283, 16Mitochondrialmembrane potentialCalciumhomeostasisOXPHOScapacityNeurogenesisSynaptic transmission15, 291AKT3AKTNOS3522, 339, 3226Mitochondria18, 21


Description

Explorative pathway to determine possible treatment options for Leigh Syndrome and other related mitochondrial diseases.

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Bibliography

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History

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CompareRevisionActionTimeUserComment
134481view01:09, 22 July 2024EweitzStandardize case
127362view06:55, 22 September 2023Cenna DoornbosConnected unconnected Labels
127361view06:51, 22 September 2023Cenna DoornbosLinked unlicked labels
125766view14:42, 9 March 2023DeSlRedrew cGMP GMP conversions, to hopefully solve Jenkins Issues
125748view10:10, 9 March 2023DeSlDisconnecting cGMP to GMP interaction to solve Jenkins issue
125742view08:32, 9 March 2023DeSlChanged cGMP to GMP interaction to straight line iso curved, to resolve Jenkins issue
124488view12:16, 1 November 2022Cenna DoornbosReplaced incorrectly displayed symbols in bibliography.
124487view09:07, 1 November 2022Cenna DoornbosModified description
124481view12:48, 31 October 2022Cenna Doornbos
124480view11:16, 31 October 2022Cenna DoornbosAttached disconnected joints
124462view09:32, 29 October 2022EgonwMade multiple pathways clickable
124425view10:26, 27 October 2022Cenna DoornbosModified description
124424view09:17, 27 October 2022Cenna DoornbosOntology Term : 'hypertension' added !
124423view09:16, 27 October 2022Cenna DoornbosOntology Term : 'pulmonary hypertension' added !
124422view09:13, 27 October 2022Cenna DoornbosOntology Term : 'mitochondrial disease pathway' added !
124421view09:12, 27 October 2022Cenna DoornbosOntology Term : 'impotence' added !
124420view09:05, 27 October 2022Cenna DoornbosModified description
124417view08:57, 27 October 2022Cenna Doornbos
124416view08:53, 27 October 2022Cenna Doornbos
124415view08:51, 27 October 2022Cenna DoornbosCorrected connenctivity to pathways.
124414view08:44, 27 October 2022Cenna DoornbosAdded annotation identifiers for the interactions.
124400view08:32, 26 October 2022Cenna DoornbosNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AKT1GeneProductENSG00000142208 (Ensembl)
AKT2GeneProductENSG00000105221 (Ensembl)
AKT3GeneProductENSG00000117020 (Ensembl)
AMPMetaboliteCHEBI:16027 (ChEBI)
Calcium homeostasisPathwayWP4088 (WikiPathways)
GAPDH inhibitorsMetaboliteCHEBI:70817 (ChEBI)
GAPDHGeneProductENSG00000111640 (Ensembl)
GMPMetaboliteCHEBI:17345 (ChEBI)
GSK3BGeneProductENSG00000082701 (Ensembl)
GTPMetaboliteCHEBI:37565 (ChEBI)
GUCY1A1GeneProductENSG00000164116 (Ensembl) Also known as GUCY1A3 [uniprot:Q02108].
GUCY1A2GeneProductENSG00000152402 (Ensembl)
GUCY1B1GeneProductENSG00000061918 (Ensembl) Also known as GUCY1B3 [uniprot:Q02153].
GUCY1B2GeneProductENSG00000123201 (Ensembl)
MAPK pathwayPathwayWP382 (WikiPathways)
Mitochondrial biogenesisPathwayWP3331 (WikiPathways)
Mitochondrial membrane potentialR-HSA-8949215 (Reactome)
NO-signalingPathwayWP1850 (WikiPathways)
NOS1GeneProductENSG00000089250 (Ensembl)
NOS3GeneProductENSG00000164867 (Ensembl) NOS3 is implicated in vascular smooth muscle relaxation through cGMP [PMID:1378832,PMID:20590592].
NRF1GeneProductENSG00000106459 (Ensembl)
NeurogenesisPathwayR-HSA-9675108 (Reactome)
Nitric oxideMetaboliteCHEBI:16480 (ChEBI)
OXPHOS capacityPathwayWP111 (WikiPathways)
PDE4 inhibitorsMetaboliteCHEBI:68844 (ChEBI)
PDE4AGeneProductENSG00000065989 (Ensembl)
PDE4BGeneProductENSG00000184588 (Ensembl)
PDE4CGeneProductENSG00000105650 (Ensembl)
PDE4DGeneProductENSG00000113448 (Ensembl)
PDE5GeneProductENSG00000138735 (Ensembl) PDE5 is also known as PDE5A or 'cGMP-specific 3',5'-cyclic phosphodiesterase'
PI3K CascadePathwayWP4448 (WikiPathways) AKT is activated trhough phosphorylation upon recruitement to the cell membrane
PPARGC1AGeneProductENSG00000109819 (Ensembl) Alternative name PGC1A
PRKG1GeneProductENSG00000185532 (Ensembl)
PRKNGeneProductENSG00000185345 (Ensembl)
Smooth muscle relaxationPathwayR-HSA-418457 (Reactome)
Synaptic transmissionPathwayR-HSA-112310.5 (Reactome)
TFAMGeneProductENSG00000108064 (Ensembl)
ZNF746GeneProductENSG00000181220 (Ensembl)
cGMPMetaboliteCHEBI:16356 (ChEBI)
sildenafilMetaboliteCHEBI:9139 (ChEBI)
tideglusibMetaboliteCHEBI:147398 (ChEBI)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
GTPcGMPmim-conversion4.6.1.2 (BRENDA)
Nitric oxidemim-conversion1.14.13.39 (BRENDA) The family of nitric oxide synthases produce nitric oxide (NO) from L-argine, oxigen and NAPDH [PMID:1722402,PMID:1662386].
PDE4 inhibitorsPDE4TBarCHEBI:68844 (ChEBI)
PDE4AMPmim-necessary-stimulation3.1.4.53 (BRENDA) The family of PDE4s (cAMP-specific 3',5'-cyclic phosphodiesterases) hydrolyse cAMP into AMP.
cGMPmim-conversion3.1.4.35 (BRENDA) cGMP is converted into GMP through hydrolysis by PDE5 [PMID:7870041].
sGCmim-stimulation4.6.1.2 (BRENDA) sGCs catalyze the conversion of GTP into GMP.
sildenafilPDE5TBarDB00203 (DrugBank)
tideglusibGSK3BTBarDB12129 (DrugBank) Glycogen synthase kinase 3beta (GSK3beta) tideglusib (NP031112) has anti-inflammatory and neuroprotective properties [PMID:17522320].
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