Neuroinflammation and glutamatergic signaling (WP5083)

Homo sapiens

The relation between neuroinflammation and glutamatergic signaling

Authors

Lisa Koole , Friederike Ehrhart , Lauren J. Dupuis , Eric Weitz , Finterly Hu , and Egon Willighagen

Activity

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

signaling pathway pertinent to the brain and nervous system neuropsychiatric disease pathway signaling pathway pertinent to immunity

Cell Type Ontology

microglial cell neuron astrocyte

Participants

Label Type Compact URI Comment
superoxide Metabolite chebi:18421
NH3(+) Metabolite chebi:29421
LPS Metabolite chebi:16412
H2O2 Metabolite chebi:16240
nitric oxide Metabolite chebi:16480
Acetyl-CoA Metabolite chebi:15351
glutamate Metabolite chebi:14321
glutamate Metabolite chebi:14321
L-Aspartate Metabolite chebi:17053
PHP Metabolite chebi:18110
PP3 Metabolite wikidata:Q27088431
glutamine Metabolite chebi:28300
2-oxoglutarate Metabolite chebi:16810
Mg2+ Metabolite chebi:18420
L-serine Metabolite chebi:17115
H+ Metabolite chebi:15378
D-serine Metabolite chebi:35247
cAMP Metabolite chebi:17489
1,3-diglycerides Metabolite chebi:47777
Glycine Metabolite chebi:15428
3PG Metabolite chebi:17138
1,2-diglycerides Metabolite chebi:49172
3-Phosphoserine Metabolite chebi:37712
pyruvate Metabolite chebi:15361
NAD+ Metabolite chebi:15846
Ca2+ Metabolite chebi:29108
2-ketoglutarate Metabolite chebi:16810
NADH Metabolite chebi:16908
glutamine Metabolite chebi:28300
glutamate Metabolite chebi:14321
glutamate Metabolite chebi:14321
glutamate Metabolite chebi:14321
Glycine Metabolite chebi:15428
D-serine Metabolite chebi:35247
D-serine Metabolite chebi:35247
L-serine Metabolite chebi:17115
Glycine Metabolite chebi:15428
D-serine Metabolite chebi:35247
glucose Metabolite chebi:17234
glucose Metabolite chebi:17234
glutamate Metabolite chebi:14321
IL13RA1 GeneProduct ncbigene:3597
NFKB2 GeneProduct ncbigene:4791
IL1R2 GeneProduct ncbigene:7850
LIF GeneProduct ncbigene:3976
TRAF5 GeneProduct ncbigene:7188
IL4 GeneProduct ncbigene:3565
TNFRSF1B GeneProduct ncbigene:7133
IL4R GeneProduct ncbigene:3566
GFAP GeneProduct ncbigene:2670
IL6 GeneProduct ncbigene:3569
SMAD2 GeneProduct ncbigene:4087
NGF GeneProduct ncbigene:4803
IL1A GeneProduct ncbigene:3552
IL6ST GeneProduct ncbigene:3572
IFNG GeneProduct ncbigene:3458
TGFBR2 GeneProduct ncbigene:7048
STAT3 GeneProduct ncbigene:6774
TNFRSF1A GeneProduct ncbigene:7132
BDNF GeneProduct ncbigene:627
TGFB1 GeneProduct ncbigene:7040
LTA GeneProduct ncbigene:4049
IL13 GeneProduct ncbigene:3596
IL13 GeneProduct ncbigene:3596
IL10RB GeneProduct ncbigene:3588
JAK1 GeneProduct ncbigene:3716
STAT1 GeneProduct ncbigene:6772
TGFBR3 GeneProduct ncbigene:7049
DAO GeneProduct ncbigene:1610
STAT3 GeneProduct ncbigene:6774
IL12A GeneProduct ncbigene:3592
SOCS3 GeneProduct ncbigene:9021
STAT1 GeneProduct ncbigene:6772
STAT6 GeneProduct ncbigene:6778
IL10RA GeneProduct ncbigene:3587
IRS1 GeneProduct ncbigene:3667
AKT1 GeneProduct ncbigene:207
TGFB2 GeneProduct ncbigene:7042
IL6R GeneProduct ncbigene:3570
SMAD3 GeneProduct ncbigene:4088
IL1R1 GeneProduct ncbigene:3554
TGFBR1 GeneProduct ncbigene:7046
SMAD7 GeneProduct ncbigene:4092
INSR GeneProduct ncbigene:3643
IL12B GeneProduct ncbigene:3593
FGF2 GeneProduct ncbigene:2247
NOS1 GeneProduct ncbigene:4842
TGFB3 GeneProduct ncbigene:7043
STAT6 GeneProduct ncbigene:6778
IL1B GeneProduct ncbigene:3553
SMAD4 GeneProduct ncbigene:4089
NFKB1 GeneProduct ncbigene:4790
GRIN1 GeneProduct ncbigene:2902
GRM8 GeneProduct ncbigene:2918
GRIK4 GeneProduct ncbigene:2900
GRIN2A GeneProduct ncbigene:2903
GRIK3 GeneProduct ncbigene:2899
PPP1CC GeneProduct ncbigene:5501
GRIN2D GeneProduct ncbigene:2906
GRIK5 GeneProduct ncbigene:2901
GRM7 GeneProduct ncbigene:2917
CAMKK2 GeneProduct ncbigene:10645
MAPK1 GeneProduct ncbigene:5594
SHMT1 GeneProduct ncbigene:6470
CAMK4 GeneProduct ncbigene:814
PHGDH GeneProduct ncbigene:26227
GOT1 GeneProduct ncbigene:2805
CAMK2A GeneProduct ncbigene:815
LRRC8B GeneProduct ncbigene:23507
LRRC8E GeneProduct ncbigene:80131
LRRC8A GeneProduct ncbigene:56262
SRR GeneProduct ncbigene:63826
GRIN2C GeneProduct ncbigene:2905
SLC1A4 GeneProduct ncbigene:6509
GRIA3 GeneProduct ncbigene:2892
PSPH GeneProduct ncbigene:5723
GRIA4 GeneProduct ncbigene:2893
GRIK2 GeneProduct ncbigene:2898
GRIA2 GeneProduct ncbigene:2891
GRM4 GeneProduct ncbigene:2914
GRIN3B GeneProduct ncbigene:116444
PLCB2 GeneProduct ncbigene:5330
PRKACA GeneProduct ncbigene:5566
PRKCG GeneProduct ncbigene:5582
ADCY1 GeneProduct ncbigene:107
LRRC8D GeneProduct ncbigene:55144
PSAT1 GeneProduct ncbigene:29968
PRKCB GeneProduct ncbigene:5579
PLCB1 GeneProduct ncbigene:23236
PPP1CB GeneProduct ncbigene:5500
SLC38A1 GeneProduct ncbigene:81539
SLC6A9 GeneProduct ncbigene:6536
CAMK2G GeneProduct ncbigene:818
PDHA1 GeneProduct ncbigene:5160
GRM1 GeneProduct ncbigene:2911
ADCY3 GeneProduct ncbigene:109
PRKCA GeneProduct ncbigene:5578
MAPK3 GeneProduct ncbigene:5595
CAMKK1 GeneProduct ncbigene:84254
PLCB3 GeneProduct ncbigene:5331
PPP1CA GeneProduct ncbigene:5499
NSMF GeneProduct ncbigene:26012 Synonym: Jacob
GRIN2B GeneProduct ncbigene:2904
SLC1A6 GeneProduct ncbigene:6511
SHMT2 GeneProduct ncbigene:6472
DLAT GeneProduct ncbigene:1737
DLD GeneProduct ncbigene:1738
ADCY8 GeneProduct ncbigene:114
DISC1 GeneProduct ncbigene:27185
LRRC8C GeneProduct ncbigene:84230
SLC38A2 GeneProduct ncbigene:54407
CFL1 GeneProduct ncbigene:1072
TRPM4 GeneProduct ncbigene:54795
PLCB4 GeneProduct ncbigene:5332
CAMK2B GeneProduct ncbigene:816
GRM2 GeneProduct ncbigene:2912
GRIK1 GeneProduct ncbigene:2897
CAMK2D GeneProduct ncbigene:817
GRIA1 GeneProduct ncbigene:2890
SLC1A1 GeneProduct ncbigene:6505
CALM1 GeneProduct ncbigene:801
GRIN3A GeneProduct ncbigene:116443
GLS GeneProduct ncbigene:2744
GLS2 GeneProduct ncbigene:27165
SLC17A6 GeneProduct ncbigene:57084
SLC17A7 GeneProduct ncbigene:57030
SLC38A5 GeneProduct ncbigene:92745
SLC38A3 GeneProduct ncbigene:10991
GRM5 GeneProduct ncbigene:2915
GRIN2B GeneProduct ncbigene:2904
GRIN1 GeneProduct ncbigene:2902
GRIN2C GeneProduct ncbigene:2905
GRIN2D GeneProduct ncbigene:2906
SRR GeneProduct ncbigene:63826
SLC7A10 GeneProduct ncbigene:56301
SLC7A10 GeneProduct ncbigene:56301
SLC6A9 GeneProduct ncbigene:6536
SLC2A1 GeneProduct ncbigene:6513
SLC2A3 GeneProduct ncbigene:6515
GRIA3 GeneProduct ncbigene:2892
GRIA4 GeneProduct ncbigene:2893
GRIA2 GeneProduct ncbigene:2891
GRIA1 GeneProduct ncbigene:2890
TGFB1 GeneProduct ncbigene:7040
TGFB2 GeneProduct ncbigene:7042
TGFB3 GeneProduct ncbigene:7043
LIF GeneProduct ncbigene:3976
CNTF GeneProduct ncbigene:1270
IL1B GeneProduct ncbigene:3553
TNF GeneProduct ncbigene:7124
IL10 GeneProduct ncbigene:3586
IGF1 GeneProduct ncbigene:3479
TNF GeneProduct ncbigene:7124
IL1B GeneProduct ncbigene:3553
TGFB1 GeneProduct ncbigene:7040
TGFB2 GeneProduct ncbigene:7042
TGFB3 GeneProduct ncbigene:7043
IL4 GeneProduct ncbigene:3565
IL10 GeneProduct ncbigene:3586
SLC1A2 GeneProduct ncbigene:6506
SLC1A3 GeneProduct ncbigene:6507
IL6 GeneProduct ncbigene:3569
IL1A GeneProduct ncbigene:3552
IL1B GeneProduct ncbigene:3553
TGFB1 GeneProduct ncbigene:7040
TGFB2 GeneProduct ncbigene:7042
TGFB3 GeneProduct ncbigene:7043
TNF GeneProduct ncbigene:7124
IL10 GeneProduct ncbigene:3586
IL10 GeneProduct ncbigene:3586
IL4 GeneProduct ncbigene:3565
IFNG GeneProduct ncbigene:3458
IFNGR2 GeneProduct ncbigene:3460
IFNGR1 GeneProduct ncbigene:3459
IGF1 GeneProduct ncbigene:3479
NFKB2 GeneProduct ncbigene:4791
NFKB1 GeneProduct ncbigene:4790
CREB1 GeneProduct ncbigene:1385
ARC GeneProduct ncbigene:23237
BCL2 GeneProduct ncbigene:596
FOS GeneProduct ncbigene:2353
BDNF GeneProduct ncbigene:627
NGF GeneProduct ncbigene:4803
NGF GeneProduct ncbigene:4803
NOS1 GeneProduct ncbigene:4842
TNF GeneProduct ncbigene:7124
IL6 GeneProduct ncbigene:3569
NGF GeneProduct ncbigene:4803
NOS1 GeneProduct ncbigene:4842
TNF GeneProduct ncbigene:7124
IL6 GeneProduct ncbigene:3569
SMAD7 GeneProduct ncbigene:4092
GFAP GeneProduct ncbigene:2670
SOCS3 GeneProduct ncbigene:9021
TGFB1 GeneProduct ncbigene:7040
TGFB1 GeneProduct ncbigene:7040
TGFB2 GeneProduct ncbigene:7042
TGFB2 GeneProduct ncbigene:7042
TGFB3 GeneProduct ncbigene:7043
TGFB3 GeneProduct ncbigene:7043
BDNF GeneProduct ncbigene:627
BDNF GeneProduct ncbigene:627
NGF GeneProduct ncbigene:4803
FGF2 GeneProduct ncbigene:2247
NGF GeneProduct ncbigene:4803
FGF2 GeneProduct ncbigene:2247
BCL2 GeneProduct ncbigene:596
FOS GeneProduct ncbigene:2353
BDNF GeneProduct ncbigene:627
NGF GeneProduct ncbigene:4803
ARC GeneProduct ncbigene:23237
BCL2 GeneProduct ncbigene:596
FOS GeneProduct ncbigene:2353
BDNF GeneProduct ncbigene:627
NGF GeneProduct ncbigene:4803
ARC GeneProduct ncbigene:23237
GS Protein uniprot:P15104

References

  1. Neuroprotective strategies for NMDAR-mediated excitotoxicity in Huntington’s Disease. Girling KD, Wang YT. Front Biol [Internet]. 2016 Nov 17;11(6):439–58. Available from: http://dx.doi.org/10.1007/s11515-016-1425-z DOI Scholia
  2. The human blood-brain barrier glucose transporter (GLUT1) is a glucose transporter of gray matter astrocytes. Morgello S, Uson RR, Schwartz EJ, Haber RS. Glia. 1995 May;14(1):43–54. PubMed Europe PMC Scholia
  3. Alteration of second messengers during acute cerebral ischemia - adenylate cyclase, cyclic AMP-dependent protein kinase, and cyclic AMP response element binding protein. Tanaka K. Prog Neurobiol. 2001 Oct;65(2):173–207. PubMed Europe PMC Scholia
  4. How calcium inhibits the magnesium-dependent enzyme human phosphoserine phosphatase. Peeraer Y, Rabijns A, Collet JF, Van Schaftingen E, De Ranter C. Eur J Biochem. 2004 Aug;271(16):3421–7. PubMed Europe PMC Scholia
  5. Smads keep TABs on inflammation. Seth RB, Chen ZJ. Nat Immunol. 2007 May;8(5):477–8. PubMed Europe PMC Scholia
  6. Strategies to enhance N-methyl-D-aspartate receptor-mediated neurotransmission in schizophrenia, a critical review and meta-analysis. Tsai GE, Lin PY. Curr Pharm Des. 2010;16(5):522–37. PubMed Europe PMC Scholia
  7. Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Hardingham GE, Bading H. Nat Rev Neurosci. 2010 Oct;11(10):682–96. PubMed Europe PMC Scholia
  8. Long-term potentiation and long-term depression: a clinical perspective. Bliss TVP, Cooke SF. Clinics (Sao Paulo). 2011;66 Suppl 1(Suppl 1):3–17. PubMed Europe PMC Scholia
  9. Metal toxicity at the synapse: presynaptic, postsynaptic, and long-term effects. Sadiq S, Ghazala Z, Chowdhury A, Büsselberg D. J Toxicol. 2012;2012:132671. PubMed Europe PMC Scholia
  10. IL-4 in the brain: a cytokine to remember. Gadani SP, Cronk JC, Norris GT, Kipnis J. J Immunol. 2012 Nov 1;189(9):4213–9. PubMed Europe PMC Scholia
  11. D-serine as a gliotransmitter and its roles in brain development and disease. Van Horn MR, Sild M, Ruthazer ES. Front Cell Neurosci. 2013 Apr 23;7:39. PubMed Europe PMC Scholia
  12. Metabotropic glutamate receptors for Parkinson’s disease therapy. Gasparini F, Di Paolo T, Gomez-Mancilla B. Parkinsons Dis. 2013;2013:196028. PubMed Europe PMC Scholia
  13. Extrasynaptic NMDA receptor involvement in central nervous system disorders. Parsons MP, Raymond LA. Neuron. 2014 Apr 16;82(2):279–93. PubMed Europe PMC Scholia
  14. When astrocytes become harmful: functional and inflammatory responses that contribute to Alzheimer’s disease. Avila-Muñoz E, Arias C. Ageing Res Rev. 2014 Nov;18:29–40. PubMed Europe PMC Scholia
  15. Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases. Tang Y, Le W. Mol Neurobiol. 2016 Mar;53(2):1181–94. PubMed Europe PMC Scholia
  16. DISC1, astrocytes and neuronal maturation: a possible mechanistic link with implications for mental disorders. Xia M, Zhu S, Shevelkin A, Ross CA, Pletnikov M. J Neurochem. 2016 Aug;138(4):518–24. PubMed Europe PMC Scholia
  17. Astrocytes: Key Regulators of Neuroinflammation. Colombo E, Farina C. Trends Immunol. 2016 Sep;37(9):608–20. PubMed Europe PMC Scholia
  18. Role of Atypical Chemokine Receptors in Microglial Activation and Polarization. Salvi V, Sozio F, Sozzani S, Del Prete A. Front Aging Neurosci. 2017 May 26;9:148. PubMed Europe PMC Scholia
  19. D-serine released by astrocytes in brainstem regulates breathing response to CO2 levels. Beltrán-Castillo S, Olivares MJ, Contreras RA, Zúñiga G, Llona I, von Bernhardi R, et al. Nat Commun. 2017 Oct 10;8(1):838. PubMed Europe PMC Scholia
  20. Glutamatergic synaptic plasticity and dysfunction in Alzheimer disease: Emerging mechanisms. Benarroch EE. Neurology. 2018 Jul 17;91(3):125–32. PubMed Europe PMC Scholia
  21. Astrocytic Regulation of Glutamate Transmission in Schizophrenia. Mei YY, Wu DC, Zhou N. Front Psychiatry. 2018 Nov 6;9:544. PubMed Europe PMC Scholia
  22. Deleterious Alteration of Glia in the Brain of Alzheimer’s Disease. Kim E, Otgontenger U, Jamsranjav A, Kim SS. Int J Mol Sci. 2020 Sep 12;21(18):6676. PubMed Europe PMC Scholia
  23. The Dual Role of Glutamatergic Neurotransmission in Alzheimer’s Disease: From Pathophysiology to Pharmacotherapy. Bukke VN, Archana M, Villani R, Romano AD, Wawrzyniak A, Balawender K, et al. Int J Mol Sci. 2020 Oct 9;21(20):7452. PubMed Europe PMC Scholia
  24. The Inflamed Brain in Schizophrenia: The Convergence of Genetic and Environmental Risk Factors That Lead to Uncontrolled Neuroinflammation. Comer AL, Carrier M, Tremblay MÈ, Cruz-Martín A. Front Cell Neurosci. 2020 Aug 27;14:274. PubMed Europe PMC Scholia
  25. Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes. Kwon HS, Koh SH. Transl Neurodegener. 2020 Nov 26;9(1):42. PubMed Europe PMC Scholia
  26. Astrocytes: a double-edged sword in neurodegenerative diseases. Ding ZB, Song LJ, Wang Q, Kumar G, Yan YQ, Ma CG. Neural Regen Res. 2021 Sep;16(9):1702–10. PubMed Europe PMC Scholia
  27. Metabolism of Amino Acids in Cancer. Wei Z, Liu X, Cheng C, Yu W, Yi P. Front Cell Dev Biol. 2021 Jan 12;8:603837. PubMed Europe PMC Scholia