Neuroinflammation and glutamatergic signaling (Homo sapiens)

From WikiPathways

Revision as of 08:22, 2 May 2021 by LKoole (Talk | contribs)
Jump to: navigation, search
282828283, 46, 15142861111811366, 226, 14, 2628262811263, 815157433113, 46171517212115241516172528415162466, 14231317246214152417152895, 20271259, 259209274, 211912898199, 259251, 8121272712, 20392594, 8, 2181918Glutamine-glutamate metabolismD-Serine metabolismPro-inflammatory cytokinesmim-stimulationPost-synaptic neuronLegendAnti-inflammatory factorsmim-conversionEnd-product of pathwayData node for a metaboliteMechanical StrengthPeripheral macrophages,T cells, inflammatory markersSpine shrinkagemim-inhibitionData node for a gene or its productmim-catalysisTranslocationData node for a pathwaymim-transcription-translationVesicle releaseTGFB3IL6STIL1APathwayTGFBR3TGFBR1STAT6JAK1TRAF5TGFB1TGFB2H2O2STAT3superoxideLTAIL10RANH3(+)SOCS3SMAD3GeneProductIL1R1IL13NFKB1FGF2STAT1IL12ATGFBR2IRS1IL1R2GFAPSTAT6SMAD7IL13SMAD2IL4LIFIL6STAT3TNFRSF1BIL12BCell SurvivalNGFTNFRSF1Anitric oxideIL1BSMAD4INSRIL6RIFNGBDNFLPSNFKB2DAOCell survivalIL4RIL10RBNOS1AKT1PI3K/AKT signalingMetaboliteIL13RA1STAT16, 2222156GRIN1TCA cycle3Long-term potentiation3Acetyl-CoAGRM8GRIK4GRIN2AGRIK3glutamatePPP1CCGRIN2DglutamateGRIK5GRM7L-AspartateCAMKK2MAPK1SHMT1GSCAMK4PHGDH4AATCCAMK2AGlycolysisPHPLRRC8BLRRC8ELRRC8ASRRGRIN2CPP3glutamineSLC1A44, 212-oxoglutarate8Mg2+MAPK Signaling PathwayGRIA3PSPHGRIA4GRIK2GRIA2GRM4GRIN3BPLCB2PRKACAPRKCGL-serineApoptosisADCY1LRRC8DPSAT1PRKCBH+PLCB1PPP1CBSLC38A1D-serineSLC6A921CAMK2GPDHA1GRM1ADCY3PRKCAMAPK3cAMPCAMKK1PLCB31,3-diglyceridesPPP1CANSMFGlycineGRIN2BSLC1A63PG8SHMT2DLATDLDADCY81,2-diglyceridesNeuroprotectionDISC1LRRC8CSLC38A2CFL110TRPM4PLCB4CAMK2B3-PhosphoserineGRM2GRIK1CAMK2Dpyruvate8GRIA1SLC1A1NAD+CALM1Depolarisation8GRIN3ACa2+82-ketoglutarateLong term depressionNADHglutamineGLSGLS2L-glutamateSLC17A6SLC17A7L-glutamateSLC38A5SLC38A3glutamateGRM5GRIN2BGRIN1GRIN2CGRIN2DGlycineD-serineD-serineL-serineSRRSLC7A1021SLC7A10SLC6A921Glycine21D-serine21glucoseSLC2A1SLC2A3glucoseGlycolysisGRIA3GRIA4GRIA2GRIA1TGFB1TGFB2TGFB3LIFCNTFIL1BTNFIL10IGF1TNFIL1BTGFB1TGFB2TGFB3IL4IL10glutamateSLC1A2SLC1A3IL6IL1AIL1B6, 22TGFB1TGFB2TGFB3TNF6, 22IL106, 22IL10IL4IFNG6, 22IFNGR2IFNGR1IGF1M2 Microglia M1 Microglia Resting Microglia Pre-synaptic neuronAstrocyte3, 8NFKB2NFKB1PCREB13ARCBCL2FOSBDNFNGFNGFNOS1TNFIL6NGFNOS1TNFIL622266SMAD76GFAP17SOCS3221515TGFB1TGFB1TGFB2TGFB2TGFB3TGFB3BDNFBDNFNGFFGF2NGFFGF22424242424BCL2FOSBDNFNGFARCBCL2FOSBDNFNGFARC


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.

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  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
  2. SP Gadani, JC Cronk, GT Norris, J Kipnis; ''Interleukin-4: A Cytokine to Remember''; J Immunol., 2013 PubMed Europe PMC Scholia
  3. Timothy V P Bliss, Sam F Cooke; ''Long-term potentiation and long-term depression: a clinical perspective''; Clinics (Sao Paulo)., 2011 PubMed Europe PMC Scholia
  4. Girling, K.D., Wang, Y.T.; ''Neuroprotective strategies for NMDAR-mediated excitotoxicity in Huntington’s Disease''; Frontiers in Biology, 2016 DOI Scholia
  5. Seth RB, Chen ZJ; ''Smads keep TABs on inflammation''; Nat Immunol., 2007 PubMed Europe PMC Scholia
  6. Eduardo E Benarroch; ''Glutamatergic synaptic plasticity and dysfunction in Alzheimer disease: Emerging mechanisms''; Neurology, 2018 PubMed Europe PMC Scholia
  7. Ding ZB, Song LJ, Wang Q, Kumar G, Yan YQ, Ma CG; ''Astrocytes: a double-edged sword in neurodegenerative diseases''; Neural Regen Res., 2021 PubMed Europe PMC Scholia
  8. Gasparini F, Di Paolo T, Gomez-Mancilla B; ''Metabotropic glutamate receptors for Parkinson's disease therapy''; Parkinsons Dis, 2013 PubMed Europe PMC Scholia
  9. Zhen Wei, Xiaoyi Liu, Chunming Cheng, Wei Yu, Ping Yi; ''Metabolism of Amino Acids in Cancer''; Front Cell Dev Biol., 2021 PubMed Europe PMC Scholia
  10. S Morgello, R R Uson, E J Schwartz, R S Haber; ''The human blood-brain barrier glucose transporter (GLUT1) is a glucose transporter of gray matter astrocytes''; Glia., 1995 PubMed Europe PMC Scholia
  11. Meng Xia, Shanshan Zhu, Alexey Shevelkin, Christopher A Ross, Mikhail Pletnikov; ''DISC1, astrocytes and neuronal maturation: a possible mechanistic link with implications for mental disorders''; J Neurochem., 2016 PubMed Europe PMC Scholia
  12. Yves Peeraer, Anja Rabijns, Jean-François Collet, Emile Van Schaftingen, Camiel De Ranter; ''How calcium inhibits the magnesium-dependent enzyme human phosphoserine phosphatase''; Eur J Biochem., 2004 PubMed Europe PMC Scholia
  13. Tang Y, Le W; ''''; , PubMed Europe PMC Scholia
  14. Yu-Ying Mei, Dong Chuan Wu, Ning Zhou; ''Astrocytic Regulation of Glutamate Transmission in Schizophrenia''; Front Psychiatry., 2018 PubMed Europe PMC Scholia
  15. Sanah Sadiq, Zena Ghazala, Arnab Chowdhury, Dietrich Büsselberg; ''Metal toxicity at the synapse: presynaptic, postsynaptic, and long-term effects''; J Toxicol., 2012 PubMed Europe PMC Scholia
  16. Kim E, Otgontenger U, Jamsranjav A, Kim SS; ''Deleterious Alteration of Glia in the Brain of Alzheimer's Disease''; Int J Mol Sci., 2020 PubMed Europe PMC Scholia
  17. Matthew P Parsons, Lynn A Raymond; ''Extrasynaptic NMDA receptor involvement in central nervous system disorders''; Neuron., 2014 PubMed Europe PMC Scholia
  18. Hyuk Sung Kwon, Seong-Ho Koh; ''Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes''; Transl Neurodegener., 2020 PubMed Europe PMC Scholia
  19. Guochuan E Tsai, Pao-Yen Lin; ''Strategies to enhance N-methyl-D-aspartate receptor-mediated neurotransmission in schizophrenia, a critical review and meta-analysis''; Curr Pharm Des., 2010 PubMed Europe PMC Scholia
  20. Fabrizio Gasparini, Thérèse Di Paolo, Baltazar Gomez-Mancilla; ''''; ,
  21. Giles E Hardingham, Hilmar Bading; ''Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders''; Nat Rev Neurosci., 2010 PubMed Europe PMC Scholia
  22. Comer AL, Carrier M, Tremblay MÈ, Cruz-Martín A; ''The Inflamed Brain in Schizophrenia: The Convergence of Genetic and Environmental Risk Factors That Lead to Uncontrolled Neuroinflammation''; Front Cell Neurosci., 2020 PubMed Europe PMC Scholia
  23. Avila-Muñoz E, Arias C.; ''When astrocytes become harmful: functional and inflammatory responses that contribute to Alzheimer's disease''; Ageing Res Rev., 2014 PubMed Europe PMC Scholia
  24. Emanuela Colombo, Cinthia Farina; ''Astrocytes: Key Regulators of Neuroinflammation''; Trends Immunol., 2016 PubMed Europe PMC Scholia
  25. K Tanaka; ''Alteration of second messengers during acute cerebral ischemia - adenylate cyclase, cyclic AMP-dependent protein kinase, and cyclic AMP response element binding protein''; Prog Neurobiol., 2001 PubMed Europe PMC Scholia
  26. S Beltrán-Castillo, M J Olivares 1, R A Contreras, G Zúñiga, I Llona 1, R von Bernhardi, J L Eugenín; ''D-serine released by astrocytes in brainstem regulates breathing response to CO 2 levels''; Nat Commun., 2017 PubMed Europe PMC Scholia
  27. Bukke VN, Archana M, Villani R, Romano AD, Wawrzyniak A, Balawender K, Orkisz S, Beggiato S, Serviddio G, Cassano T.; ''The Dual Role of Glutamatergic Neurotransmission in Alzheimer's Disease: From Pathophysiology to Pharmacotherapy''; Int J Mol Sci., 2020 PubMed Europe PMC Scholia
  28. Salvi V, Sozio F, Sozzani S, Del Prete A; ''Role of Atypical Chemokine Receptors in Microglial Activation and Polarization''; Front Aging Neurosci., 2017 PubMed Europe PMC Scholia

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"
Personal tools