Neuroinflammation and glutamatergic signaling (Homo sapiens)

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ArcPathVisio Brace Ellipse EndoplasmicReticulum GolgiApparatus HexagonPathVisio MimDegradation Mitochondria Octagon PentagonPathVisio Rectangle RoundedRectangle SarcoplasmicReticulum TriangleEquilateralEast TrianglePathVisio none MetabolitePathwayGeneProductmim-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 StrengthLegendIL13RA1IL4RNFKB2NFKB1IL1R2IL1R1LIFLTAIGF1TGFB1TGFB2TGFB3IL4IL10TRAF5IL4IL13TGFB1TGFB2TGFB3IL10TNFRSF1BTNFRSF1ACell SurvivalGFAPsuperoxideIL1AIL12AIL12BNOS1IL1BTNFIL1BIL6LIFCNTFSMAD2SMAD3SMAD4NGFBDNFTGFB1TGFB2FGF2TGFB3IL6STIL6RIFNGLPSTGFBR2TGFBR3TGFBR1PI3K/AKT signalingSTAT3STAT6NH3(+)H2O2IL13IL10IL4IL10RBIL10RAJAK1STAT1NFKB2NFKB1DAOSTAT3SOCS3STAT1IRS1AKT1SMAD7INSRSTAT6Cell survivalNeuroprotectionnitric oxideIL1BTNFIL6GRIN1GRIN2AGRIN2DGRIN2CGRIN3BGRIN2BGRIN3ATCA cycleLong-term potentiationAcetyl-CoAGRM8GRM7GRM4GRM2GRIK4GRIK3GRIK5GRIK2GRIK1glutamatePPP1CCPPP1CBPPP1CAglutamateL-AspartateCAMKK2CAMKK1MAPK1MAPK3SHMT1SHMT2GSCAMK4PHGDHGOT1CAMK2ACAMK2GCAMK2BCAMK2DGlycolysisPHPLRRC8BLRRC8ELRRC8ALRRC8DLRRC8CSRRPP3glutamineSLC1A42-oxoglutarateMg2+MAPK Signaling PathwayGRIA3GRIA4GRIA2GRIA1PSPHPLCB2PLCB1PLCB3PLCB4PRKACAPRKCGPRKCBPRKCAL-serineApoptosisADCY1ADCY3ADCY8PSAT1H+NADHSLC38A1SLC38A2D-serineSLC6A9PDHA1DLATDLDGRM1GRM5cAMP1,3-diglycerides1,2-diglyceridesNSMFGlycineSLC1A6SLC1A13PGDISC1CFL1TRPM4GRIN2BGRIN1GRIN2CGRIN2D3-PhosphoserinepyruvateNAD+CALM1DepolarisationCa2+2-ketoglutarateLong term depressionglutamineGLSGLS2glutamateSLC17A6SLC17A7glutamateSLC38A5SLC38A3glutamateGlycineD-serineD-serineL-serineSRRSLC7A10SLC7A10SLC6A9GlycineD-serineglucoseSLC2A1SLC2A3glucoseGlycolysisGRIA3GRIA4GRIA2GRIA1glutamateSLC1A2SLC1A3IL1AIL1BTGFB1TGFB2TGFB3TNFIL10IFNGIFNGR2IFNGR1IGF1M2 MicrogliaM1 MicrogliaResting MicrogliaPre-synaptic neuronAstrocytePCREB1ARCBCL2FOSBDNFNGFNGFNOS1TNFIL6NGFNOS1TNFIL6SMAD7GFAPSOCS3TGFB1TGFB1TGFB2TGFB3BDNFNGFFGF2TGFB2TGFB3BDNFNGFFGF2BCL2FOSBDNFNGFARCBCL2FOSBDNFNGFARCGlutamine-glutamate metabolismProtein biosynthesisProtein biosynthesisProtein biosynthesisName: Neuroinflammation and glutamatergic signalingOrganism: Homo sapiens


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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  1. Marion R Van Horn, Mari Sild, Edward S Ruthazer; ''D-serine as a gliotransmitter and its roles in brain development and disease''; Front Cell Neurosci., 2013 PubMed Europe PMC Scholia
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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...
Name  ↓Type  ↓Database reference  ↓Comment  ↓
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

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