Neuroinflammation and glutamatergic signaling (Homo sapiens)

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3, 7283, 20241036, 10272810, 11, 27242010, 123, 2011102812324247282124101132812PathwayGeneProductMetabolite2424242424232781620812162510, 2712215122121591012162212161092241318, 2219488, 13131813199, 204134241374138, 131384, 74919191, 183138137, 9, 207145mim-catalysismim-stimulationPeripheral macrophages,T cells, inflammatory markersData node for a pathwaySpine shrinkageTranslocationVesicle releaseEnd-product of pathwayD-Serine metabolismPost-synaptic neuronData node for a metabolitemim-transcription-translationPro-inflammatory factorsmim-inhibitionmim-conversionAnti-inflammatory factorsData node for a gene or its productMechanical StrengthLegendIL13RA1NFKB2IL1R2LIFTRAF5IL4TNFRSF1BIL4RCell SurvivalGFAPsuperoxide6IL6SMAD26, 10NGFIL1AIL6STIFNGTGFBR2PI3K/AKT signalingSTAT3TNFRSF1ANH3(+)BDNFTGFB1LTAIL13IL13IL10RBJAK1STAT1TGFBR3DAOSTAT3IL12A10SOCS3STAT1STAT6IL10RAIRS1AKT1TGFB2IL6RSMAD3IL1R1TGFBR1SMAD7INSR12IL12BFGF2NOS1TGFB3STAT6LPSCell survivalIL1BSMAD4H2O2nitric oxideNFKB1GRIN1TCA cycleLong-term potentiation33Acetyl-CoAGRM8GRIK4GRIN2AGRIK3glutamatePPP1CCGRIN2DglutamateGRIK5GRM7L-AspartateCAMKK2MAPK1SHMT1GSCAMK4PHGDH20GOT1CAMK2AGlycolysisPHPLRRC8BLRRC8ELRRC8ASRRGRIN2CPP3glutamineSLC1A49, 202-oxoglutarateMg2+7MAPK Signaling PathwayGRIA3PSPHGRIA4GRIK2GRIA2GRM4GRIN3BPLCB2PRKACAPRKCGL-serineApoptosisADCY1LRRC8DPSAT1PRKCBH+PLCB1PPP1CBSLC38A1D-serineSLC6A99CAMK2GPDHA1GRM1ADCY3PRKCAMAPK3cAMPCAMKK1PLCB31,3-diglyceridesPPP1CANSMFGlycineGRIN2BSLC1A63PG7SHMT2DLATDLDADCY81,2-diglyceridesNeuroprotectionDISC1LRRC8CSLC38A2CFL126TRPM4PLCB4CAMK2B3-PhosphoserineGRM2GRIK1CAMK2Dpyruvate7GRIA1SLC1A1NAD+CALM1DepolarisationGRIN3A7Ca2+72-ketoglutarateLong term depressionNADHglutamineGLSGLS2glutamateSLC17A6SLC17A7glutamateSLC38A5SLC38A3glutamateGRM5GRIN2BGRIN1GRIN2CGRIN2DGlycineD-serineD-serineL-serineSRRSLC7A109SLC7A10SLC6A99Glycine9D-serineglucose9SLC2A1SLC2A3glucoseGlycolysisGRIA3GRIA4GRIA2GRIA1TGFB1TGFB2TGFB3LIFCNTFIL1BTNFIL10IGF1TNFIL1BTGFB1TGFB2TGFB3IL4IL10glutamateSLC1A2SLC1A3IL6IL1AIL1B6, 10TGFB1TGFB2TGFB3TNF6, 10IL106, 10IL10IL4IFNGIFNGR26, 10IFNGR1IGF1M2 Microglia M1 Microglia Resting Microglia Pre-synaptic neuronAstrocyte3, 7NFKB2NFKB1PCREB13ARCBCL2FOSBDNFNGFNGFNOS1TNFIL6NGFNOS1TNFIL6252525SMAD72GFAP6SOCS312TGFB112TGFB1TGFB2TGFB2TGFB3TGFB3BDNFBDNFNGFFGF2NGFFGF21616161616BCL2FOSBDNFNGFARCBCL2FOSBDNFNGFARCGlutamine-glutamate metabolismProtein biosynthesisProtein biosynthesisProtein biosynthesis


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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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


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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)
ADCY1GeneProduct107 (Entrez Gene)
ADCY3GeneProduct109 (Entrez Gene)
ADCY8GeneProduct114 (Entrez Gene)
AKT1GeneProduct207 (Entrez Gene)
ARCGeneProduct23237 (Entrez Gene)
Acetyl-CoAMetaboliteCHEBI:15351 (ChEBI)
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)
GOT1GeneProduct2805 (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)
GlycineMetaboliteCHEBI:15428 (ChEBI)
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-AspartateMetaboliteCHEBI:17053 (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 depressionPathwayQ1517140 (Wikidata)
Long-term potentiationPathwayQ1805481 (Wikidata)
MAPK Signaling PathwayPathwayWP382 (WikiPathways)
MAPK1GeneProduct5594 (Entrez Gene)
MAPK3GeneProduct5595 (Entrez Gene)
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)
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

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