Neuroinflammation and glutamatergic signaling (Homo sapiens)

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17171717124242484184, 2416288, 265, 241718198, 262481826178, 191812, 24, 281728188144106642712, 2412642426427422212711271725274212411617137, 152311010, 13137132321, 26113117131911310, 1313101, 1912123237, 9813101319, 21, 261932Post-synaptic neuronmim-inhibitionPeripheral macrophages,T cells, inflammatory markersData node for a metaboliteGlutamine-glutamate metabolismData node for a gene or its productAnti-inflammatory factorsD-Serine metabolismmim-transcription-translationLegendData node for a pathwayTranslocationmim-conversionmim-catalysisMechanical Strengthmim-stimulationVesicle releaseSpine shrinkagePro-inflammatory cytokinesEnd-product of pathwayGFAPIL12BSMAD2IL6TGFB3IL4RIL10RBIL6RSOCS3IL13NFKB2NH3(+)H2O2IL10RACell survivalnitric oxideSTAT1BDNFMetabolitePI3K/AKT signalingDAOAKT1TNFRSF1ATGFB2GeneProductSMAD4SMAD7IL13TGFBR3IL1ASTAT1NFKB1TNFRSF1BFGF2SMAD3Cell SurvivalIL13RA1TGFB1IL1R2IFNGLIFTGFBR1IL4superoxideTGFBR2IL1BLPSPathwayIL1R1IRS1NGFSTAT3NOS1JAK1STAT6TRAF5LTAINSRSTAT6IL6STSTAT3IL12A2445, 245GRIN1TCA cycle8Long-term potentiation8Acetyl-CoAGRM8GRIK4GRIN2AGRIK3glutamatePPP1CCGRIN2DglutamateGRIK5GRM7L-AspartateCAMKK2MAPK1SHMT1GSCAMK4PHGDH26AATCCAMK2AGlycolysisPHPLRRC8BLRRC8ELRRC8ASRRGRIN2CPP3glutamineSLC1A421, 262-oxoglutarate19Mg2+MAPK Signaling PathwayGRIA3PSPHGRIA4GRIK2GRIA2GRM4GRIN3BPLCB2PRKACAPRKCGL-serineApoptosisADCY1LRRC8DPSAT1PRKCBH+PLCB1PPP1CBSLC38A1D-serineSLC6A921CAMK2GPDHA1GRM1ADCY3PRKCAMAPK3cAMPCAMKK1PLCB31,3-diglyceridesPPP1CANSMFGlycineGRIN2BSLC1A63PG19SHMT2DLATDLDADCY81,2-diglyceridesNeuroprotectionDISC1LRRC8CSLC38A2CFL120TRPM4PLCB4CAMK2B3-PhosphoserineGRM2GRIK1CAMK2Dpyruvate19GRIA1SLC1A1NAD+CALM1Depolarisation19GRIN3ACa2+192-ketoglutarateLong term depressionNADHglutamineGLSGLS2L-glutamateSLC17A6SLC17A7L-glutamateSLC38A5SLC38A3glutamateGRM5GRIN2BGRIN1GRIN2CGRIN2DGlycineD-serineD-serineL-serineSRRSLC7A1021SLC7A10SLC6A921Glycine21D-serine21glucoseSLC2A1SLC2A3glucoseGlycolysisGRIA3GRIA4GRIA2GRIA1TGFB1TGFB2TGFB3LIFCNTFIL1BTNFIL10IGF1TNFIL1BTGFB1TGFB2TGFB3IL4IL10glutamateSLC1A2SLC1A3IL6IL1AIL1B5, 24TGFB1TGFB2TGFB3TNF5, 24IL105, 24IL10IL4IFNG5, 24IFNGR2IFNGR1IGF1M2 Microglia M1 Microglia Resting Microglia Pre-synaptic neuronAstrocyte8, 19NFKB2NFKB1PCREB18ARCBCL2FOSBDNFNGFNGFNOS1TNFIL6NGFNOS1TNFIL6252525242424SMAD7GFAP27SOCS3544TGFB1TGFB1TGFB2TGFB2TGFB3TGFB3BDNFBDNFNGFFGF2NGFFGF266666BCL2FOSBDNFNGFARCBCL2FOSBDNFNGFARC


Description

Pre-synaptic neurons release glutamate, which acts on various receptors (kainate, metabotropic, AMPA and NMDA), thereby regulating LTP, LDP, neuronal survival and proliferation. Glutamate retro-signaling negatively regulates its exocytotic release. The remainder of glutamate is taken up by astrocytes through EAAT1-4. Glutamine is generated from blood-derived glucose, transported to pre-synaptic neurons and converted into glutamate. Alternatively, glucose is converted into D-serine, which functions as co-agonist for NMDARs and is broken down by DAAO. CNS inflammation induces M1 and M2 microglia, which modulate neuronal and astrocyte function.

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Bibliography

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History

View all...
CompareRevisionActionTimeUserComment
135193view00:21, 8 August 2024EweitzRefine legend
135192view00:19, 8 August 2024EweitzEconomize layout
129067view03:00, 10 March 2024EweitzOntology Term : 'glial cell' added !
120385view08:07, 30 November 2021EgonwMade several pathways clickable
119096view08:47, 17 June 2021FinterlyAdd DOI information for PublicationXref
118960view10:47, 5 June 2021EweitzOntology Term : 'astrocyte' added !
118959view10:46, 5 June 2021EweitzOntology Term : 'neuron' added !
118958view10:46, 5 June 2021EweitzOntology Term : 'microglial cell' added !
116348view08:35, 3 May 2021LKooleOntology Term : 'signaling pathway pertinent to immunity' added !
116346view08:06, 3 May 2021LKooleAnnotated nodes
116345view07:37, 3 May 2021LKooleEdits to layout. Added protein biosynthesis groups.
116338view12:23, 2 May 2021L DupuisConnected lines
116337view11:54, 2 May 2021LKooleAddition transcription-translation interactions
116336view08:22, 2 May 2021LKooleMinor edits to connections, annotations and interactions. Addition of CREB1 transcription
116311view12:45, 29 April 2021LKooleOntology Term : 'neuropsychiatric disease pathway' added !
116310view12:44, 29 April 2021FehrhartOntology Term : 'signaling pathway pertinent to the brain and nervous system' added !
116301view09:10, 29 April 2021LKooleModified description
116300view08:55, 29 April 2021LKooleAdded a legend. Connected unlinked data nodes. Changed colours of borders. Made transportation/release arrows dark blue. Changed interactions to make them consistent with legend.
116259view09:12, 22 April 2021LKooleNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
1,2-diglyceridesMetaboliteCHEBI:49172 (ChEBI)
1,3-diglyceridesMetaboliteCHEBI:47777 (ChEBI)
2-ketoglutarateMetaboliteCHEBI:16810 (ChEBI)
2-oxoglutarateMetaboliteCHEBI:16810 (ChEBI)
3-PhosphoserineMetaboliteCHEBI:37712 (ChEBI)
3PGMetaboliteCHEBI:17138 (ChEBI)
AATCProteinA0A140VK69 (Uniprot-TrEMBL)
ADCY1GeneProduct107 (Entrez Gene)
ADCY3GeneProduct109 (Entrez Gene)
ADCY8GeneProduct114 (Entrez Gene)
AKT1GeneProduct207 (Entrez Gene)
ARCGeneProduct23237 (Entrez Gene)
Acetyl-CoAMetaboliteHMDB01206 (HMDB)
ApoptosisPathwayWP254 (WikiPathways)
BCL2GeneProduct596 (Entrez Gene)
BDNFGeneProduct627 (Entrez Gene)
CALM1GeneProduct801 (Entrez Gene)
CAMK2AGeneProduct815 (Entrez Gene)
CAMK2BGeneProduct816 (Entrez Gene)
CAMK2DGeneProduct817 (Entrez Gene)
CAMK2GGeneProduct818 (Entrez Gene)
CAMK4GeneProduct814 (Entrez Gene)
CAMKK1GeneProduct84254 (Entrez Gene)
CAMKK2GeneProduct10645 (Entrez Gene)
CFL1GeneProduct1072 (Entrez Gene)
CNTFGeneProduct1270 (Entrez Gene)
CREB1GeneProduct1385 (Entrez Gene)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Cell SurvivalPathwayQ70690408 (Wikidata)
Cell survivalPathwayQ70690408 (Wikidata)
D-serineMetaboliteCHEBI:35247 (ChEBI)
DAOGeneProduct1610 (Entrez Gene)
DISC1GeneProduct27185 (Entrez Gene)
DLATGeneProduct1737 (Entrez Gene)
DLDGeneProduct1738 (Entrez Gene)
DepolarisationPathwayQ14864044 (Wikidata)
FGF2GeneProduct2247 (Entrez Gene)
FOSGeneProduct2353 (Entrez Gene)
GFAPGeneProduct2670 (Entrez Gene)
GLS2GeneProduct27165 (Entrez Gene)
GLSGeneProduct2744 (Entrez Gene)
GRIA1GeneProduct2890 (Entrez Gene)
GRIA2GeneProduct2891 (Entrez Gene)
GRIA3GeneProduct2892 (Entrez Gene)
GRIA4GeneProduct2893 (Entrez Gene)
GRIK1GeneProduct2897 (Entrez Gene)
GRIK2GeneProduct2898 (Entrez Gene)
GRIK3GeneProduct2899 (Entrez Gene)
GRIK4GeneProduct2900 (Entrez Gene)
GRIK5GeneProduct2901 (Entrez Gene)
GRIN1GeneProduct2902 (Entrez Gene)
GRIN2AGeneProduct2903 (Entrez Gene)
GRIN2BGeneProduct2904 (Entrez Gene)
GRIN2CGeneProduct2905 (Entrez Gene)
GRIN2DGeneProduct2906 (Entrez Gene)
GRIN3AGeneProduct116443 (Entrez Gene)
GRIN3BGeneProduct116444 (Entrez Gene)
GRM1GeneProduct2911 (Entrez Gene)
GRM2GeneProduct2912 (Entrez Gene)
GRM4GeneProduct2914 (Entrez Gene)
GRM5GeneProduct2915 (Entrez Gene)
GRM7GeneProduct2917 (Entrez Gene)
GRM8GeneProduct2918 (Entrez Gene)
GSProteinP15104 (Uniprot-TrEMBL)
GeneProductGeneProduct
GlycineMetaboliteHMDB00123 (HMDB)
GlycolysisPathwayWP534 (WikiPathways)
H+MetaboliteCHEBI:15378 (ChEBI)
H2O2MetaboliteCHEBI:16240 (ChEBI)
IFNGGeneProduct3458 (Entrez Gene)
IFNGR1GeneProduct3459 (Entrez Gene)
IFNGR2GeneProduct3460 (Entrez Gene)
IGF1GeneProduct3479 (Entrez Gene)
IL10GeneProduct3586 (Entrez Gene)
IL10RAGeneProduct3587 (Entrez Gene)
IL10RBGeneProduct3588 (Entrez Gene)
IL12AGeneProduct3592 (Entrez Gene)
IL12BGeneProduct3593 (Entrez Gene)
IL13GeneProduct3596 (Entrez Gene)
IL13RA1GeneProduct3597 (Entrez Gene)
IL1AGeneProduct3552 (Entrez Gene)
IL1BGeneProduct3553 (Entrez Gene)
IL1R1GeneProduct3554 (Entrez Gene)
IL1R2GeneProduct7850 (Entrez Gene)
IL4GeneProduct3565 (Entrez Gene)
IL4RGeneProduct3566 (Entrez Gene)
IL6GeneProduct3569 (Entrez Gene)
IL6RGeneProduct3570 (Entrez Gene)
IL6STGeneProduct3572 (Entrez Gene)
INSRGeneProduct3643 (Entrez Gene)
IRS1GeneProduct3667 (Entrez Gene)
JAK1GeneProduct3716 (Entrez Gene)
L-AspartateMetabolite
L-glutamateMetaboliteCHEBI:29985 (ChEBI)
L-serineMetaboliteCHEBI:17115 (ChEBI)
LIFGeneProduct3976 (Entrez Gene)
LPSMetaboliteCHEBI:16412 (ChEBI)
LRRC8AGeneProduct56262 (Entrez Gene)
LRRC8BGeneProduct23507 (Entrez Gene)
LRRC8CGeneProduct84230 (Entrez Gene)
LRRC8DGeneProduct55144 (Entrez Gene)
LRRC8EGeneProduct80131 (Entrez Gene)
LTAGeneProduct4049 (Entrez Gene)
Long term depressionPathway
Long-term potentiationPathwayQ1805481 (Wikidata)
MAPK Signaling PathwayPathwayWP382 (WikiPathways)
MAPK1GeneProduct5594 (Entrez Gene)
MAPK3GeneProduct5595 (Entrez Gene)
MetaboliteMetabolite
Mg2+MetaboliteCHEBI:18420 (ChEBI)
NAD+MetaboliteCHEBI:15846 (ChEBI)
NADHMetaboliteCHEBI:16908 (ChEBI)
NFKB1GeneProduct4790 (Entrez Gene)
NFKB2GeneProduct4791 (Entrez Gene)
NGFGeneProduct4803 (Entrez Gene)
NH3(+)MetaboliteCHEBI:29421 (ChEBI)
NOS1GeneProduct4842 (Entrez Gene)
NSMFGeneProduct26012 (Entrez Gene) Synonym: Jacob
NeuroprotectionPathwayQ1981368 (Wikidata)
PDHA1GeneProduct5160 (Entrez Gene)
PHGDHGeneProduct26227 (Entrez Gene)
PHPMetaboliteCHEBI:18110 (ChEBI)
PI3K/AKT signalingPathwayWP2653 (WikiPathways)
PLCB1GeneProduct23236 (Entrez Gene)
PLCB2GeneProduct5330 (Entrez Gene)
PLCB3GeneProduct5331 (Entrez Gene)
PLCB4GeneProduct5332 (Entrez Gene)
PP3MetaboliteQ27088431 (Wikidata)
PPP1CAGeneProduct5499 (Entrez Gene)
PPP1CBGeneProduct5500 (Entrez Gene)
PPP1CCGeneProduct5501 (Entrez Gene)
PRKACAGeneProduct5566 (Entrez Gene)
PRKCAGeneProduct5578 (Entrez Gene)
PRKCBGeneProduct5579 (Entrez Gene)
PRKCGGeneProduct5582 (Entrez Gene)
PSAT1GeneProduct29968 (Entrez Gene)
PSPHGeneProduct5723 (Entrez Gene)
PathwayPathway
SHMT1GeneProduct6470 (Entrez Gene)
SHMT2GeneProduct6472 (Entrez Gene)
SLC17A6GeneProduct57084 (Entrez Gene)
SLC17A7GeneProduct57030 (Entrez Gene)
SLC1A1GeneProduct6505 (Entrez Gene)
SLC1A2GeneProduct6506 (Entrez Gene)
SLC1A3GeneProduct6507 (Entrez Gene)
SLC1A4GeneProduct6509 (Entrez Gene)
SLC1A6GeneProduct6511 (Entrez Gene)
SLC2A1GeneProduct6513 (Entrez Gene)
SLC2A3GeneProduct6515 (Entrez Gene)
SLC38A1GeneProduct81539 (Entrez Gene)
SLC38A2GeneProduct54407 (Entrez Gene)
SLC38A3GeneProduct10991 (Entrez Gene)
SLC38A5GeneProduct92745 (Entrez Gene)
SLC6A9GeneProduct6536 (Entrez Gene)
SLC7A10GeneProduct56301 (Entrez Gene)
SMAD2GeneProduct4087 (Entrez Gene)
SMAD3GeneProduct4088 (Entrez Gene)
SMAD4GeneProduct4089 (Entrez Gene)
SMAD7GeneProduct4092 (Entrez Gene)
SOCS3GeneProduct9021 (Entrez Gene)
SRRGeneProduct63826 (Entrez Gene)
STAT1GeneProduct6772 (Entrez Gene)
STAT3GeneProduct6774 (Entrez Gene)
STAT6GeneProduct6778 (Entrez Gene)
TCA cyclePathwayWP78 (WikiPathways)
TGFB1GeneProduct7040 (Entrez Gene)
TGFB2GeneProduct7042 (Entrez Gene)
TGFB3GeneProduct7043 (Entrez Gene)
TGFBR1GeneProduct7046 (Entrez Gene)
TGFBR2GeneProduct7048 (Entrez Gene)
TGFBR3GeneProduct7049 (Entrez Gene)
TNFGeneProduct7124 (Entrez Gene)
TNFRSF1AGeneProduct7132 (Entrez Gene)
TNFRSF1BGeneProduct7133 (Entrez Gene)
TRAF5GeneProduct7188 (Entrez Gene)
TRPM4GeneProduct54795 (Entrez Gene)
cAMPMetaboliteCHEBI:17489 (ChEBI)
glucoseMetaboliteCHEBI:17234 (ChEBI)
glutamateMetaboliteCHEBI:14321 (ChEBI)
glutamineMetaboliteCHEBI:28300 (ChEBI)
nitric oxideMetaboliteCHEBI:16480 (ChEBI)
pyruvateMetaboliteCHEBI:15361 (ChEBI)
superoxideMetaboliteCHEBI:18421 (ChEBI)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP5083"
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