Spinal Cord Injury (Homo sapiens)

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14C1QBTNFSF13CSPG4FECHP1LTBPLXNA2CDC42LTB4TNFSF13BAQP1LEPCD47NGFRMIFPTPRZ1NOPDYNLGALS3APEX1LTB4RAIF12726534934363030452471812AstroctyeSpinal Cord InjuryTimePro-InflammatoryFactorsZFP36FCGR2APRB1PTPRAIL1BZFP36NOS2TNFNR4A120IL4BTG2BTG2FBRCDK2NOS1IL2TNFIL6TLR4FOSIL1BTGFB1TLR4TNFEGR1FOSMMP12IFNGGlial ScarAstrocyte GliosisSwelling/EdemaMBPAntigens ReleasedRTN4C5CXCL1Neutrophil Chemoattractants11, 46CXCL8NeurtrophilsMonocytesAQP442TTLegendTT:Therapeutic Target (increase)TTTTTT:Therapeutic Target (decrease)T-CellsB-CellsB Cell Stimulating16Activated Microglia/Macrophages(Transient)RepairIL1BNOS2TNFARG1TOXIC FERROUSIRONFocal Adensions29, 54EPHA4TTEPHNB2TTTTTTTTCXCL10Neuro protectionAntibody ReleaseNeuronalInjuryResponseAstrocyteInjuryResponseG1-S Cell Cycle Re-entry (TT)28CCNG1MicrogliaMicrogliaActivationAxonal RetractionRecruitmentRecruitmentMMP9TT50Chondroitin Sulfate ProteoglycansNCAN44SLIT1Axon Retraction44SLIT2SLIT3NTN1RGMATTTTTTTTTTMMP9MMP95050MMP9TT50TTTTCCR2IL1R1TT46ECM BreakdownECM BreakdownIL1ACXCL1Monocyte ChemoattractantsCXCL211, 46CCL2OligodendrocyteInjury ResponsePLA2G6PLA2G5PLA2G2AmelittinInflammationDemyelinationANXA19TTTTTTTTRed Blood CellsMyelinEndothelial LeukocyteAdehsion Factors51ICAM1SELPTTTTPlasticityKLK8TT33MicrogliaActivated Microglia/MacrophagesActivated Microglia/MacrophagesGFAP50TTIntermediateFillament3CDK4TACR1E2F5RB1PRKCAE2F1MAPK1CCND1MYCGADD45AMAPK3TTTTTTAstroctyeNeuron & OligodendrocyteApoptosis/NecrosisMicrogliaProliferationTP53CytotoxicCytotoxicCHST11VCANCOL4A1XYLT1COL2A1ACANBCANGlial Scar FromationSOX9Axonal GrowthInhibition3IgG, IgMTP53TT14TTTTGRIN1VIM3919TTT Cell Stimulating16FK50613PPP3CATTFK50623FK50623GAP43TTFK50623Axonal RegenerationFKBP1AIL2C3 ToxinC1Q and Fc receptive cellsMAGRTN4RHOARHOCRHOBROCK2OMGRTN4RLILRB331MyelinInjury ResponseArachidonic acidPGH2PTGS243TT25ROSNOX4MIR23BOlomoucine8CDK1GDNF2TTSEMA6A12TTAxonal GrowthInhibitionGJA1ATP-Release41TTBDNFTTImmediate Response Genes282-MethoxyestradiolTT24RAC1TTTTAstroctyeFOXO3TT10CDKN1B10TTN2 Glial Precursor21EGFRPD 16839315TT52CASP3TTTTMotor NeuronOligodendrocyte


Description

This pathway provides an overview of cell types, therapeutic targets, drugs, new proposed targets and pathways implicated in spinal cord injury. Spinal cord injury is a complex multistep process that involves the regulation of gene expression and signaling in motor neurons, oligodentrocytes, microglia, and astrocytes that trigger immediate immune responses lasting several weeks. Within 24 hours, chemoattractants and cytokines released from the site of injury activate neutrophils which further recruit B and T cells or recruit monocytes that ultimately result in infiltration and activation by microglia and macrophages. These immune responses result in inflammation, excitotoxicity, cell death, formation of glial scar, and suppression of axonal regeneration. An increase in the expression of cell cycle genes further results in proliferation of astrocytes and microglia that leads to apoptosis and necrosis of oligodentrocytes and neurons. An example therapy is the administration of the immunosuppressant FK506, also used in transplantation to offer neuroprotection. Proteins on this pathway have targeted assays available via the CPTAC Assay Portal.

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Bibliography

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History

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CompareRevisionActionTimeUserComment
106712view13:15, 17 September 2019MaintBotHMDB identifier normalization
105820view23:01, 15 August 2019KhanspersModified description
104858view14:59, 20 June 2019DeSlRemoved weird signs in lit. ref (part 1)
104853view14:52, 20 June 2019DeSlUpdated empty lit. ref
104850view14:46, 20 June 2019DeSlCOnnected unconnected lines.
104843view14:33, 20 June 2019DeSlChanged lines for motor neuron to graphical lines.
101932view12:38, 18 November 2018EgonwRemoved whitespace in PubMed identifiers.
87678view08:55, 25 July 2016LindarieswijkOntology Term : 'disease pathway' added !
84650view22:21, 10 March 2016Khanspersupdated mmp12 xref
80343view18:15, 9 June 2015Khanspersupdated color and type for MIR23B
79963view13:55, 28 April 2015Zaricorected annotation PTGS2 from chimpanzee to human, annotated Ros
79931view12:14, 27 April 2015EveloRenamed IL8 with the new official HGNC name CXCL8
78556view10:31, 7 January 2015MaintBotadded missing graphIds
76332view08:13, 2 July 2014MkutmonFixed annotation for C5
74098view22:56, 29 March 2014Ariuttaupdate arrowhead
69988view22:03, 11 July 2013MaintBotupdating to 2013 schema
59143view00:06, 22 February 2013DMicaelSpecify description
59080view21:55, 21 February 2013MaintBotUpdated Ensembl data source
58412view22:54, 12 February 2013NsalomonisSpecify description
58411view22:50, 12 February 2013DMicaelSpecify description
58410view22:46, 12 February 2013NsalomonisSpecify description
58380view21:35, 12 February 2013DMicaelPeriodical save, work in progress
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58349view16:11, 12 February 2013NsalomonisSpecify description
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58287view19:51, 11 February 2013DMicaelPeriodical save, work in progress
57006view14:04, 19 January 2013EgonwCorrected to the correct PubChem-compound data source.
56064view04:05, 1 January 2013NsalomonisModified description
55915view23:04, 27 December 2012MaintBotModified categories
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External references

DataNodes

View all...
NameTypeDatabase referenceComment
2-MethoxyestradiolMetabolite66414 (PubChem-compound)
ACANGeneProductENSG00000157766 (Ensembl)
AIF1GeneProduct199 (Entrez Gene)
ANXA1GeneProductENSG00000135046 (Ensembl)
APEX1GeneProductENSG00000100823 (Ensembl)
AQP1GeneProductENSG00000240583 (Ensembl)
AQP4GeneProductENSG00000171885 (Ensembl)
ARG1GeneProductENSG00000118520 (Ensembl)
Arachidonic acidMetaboliteHMDB0001043 (HMDB)
BCANGeneProductENSG00000132692 (Ensembl)
BDNFGeneProductENSG00000176697 (Ensembl)
BTG2GeneProductENSG00000159388 (Ensembl)
C1QBGeneProductENSG00000173369 (Ensembl)
C5GeneProductENSG00000106804 (Ensembl)
CASP3GeneProductENSG00000164305 (Ensembl)
CCL2GeneProductENSG00000108691 (Ensembl)
CCND1GeneProductENSG00000110092 (Ensembl)
CCNG1GeneProductENSG00000113328 (Ensembl)
CCR2GeneProductENSG00000121807 (Ensembl)
CD47GeneProductENSG00000196776 (Ensembl)
CDC42GeneProductENSG00000070831 (Ensembl)
CDK1GeneProductENSG00000170312 (Ensembl)
CDK2GeneProductENSG00000123374 (Ensembl)
CDK4GeneProductENSG00000135446 (Ensembl)
CDKN1BGeneProductENSG00000111276 (Ensembl)
CHST11GeneProductENSG00000171310 (Ensembl)
COL2A1GeneProductENSG00000139219 (Ensembl)
COL4A1GeneProductENSG00000187498 (Ensembl)
CSPG4GeneProductENSG00000173546 (Ensembl)
CXCL10GeneProductENSG00000169245 (Ensembl)
CXCL1GeneProductENSG00000163739 (Ensembl)
CXCL2GeneProductENSG00000081041 (Ensembl)
CXCL8GeneProductENSG00000169429 (Ensembl)
E2F1GeneProductENSG00000101412 (Ensembl)
E2F5GeneProductENSG00000133740 (Ensembl)
EGFRGeneProductENSG00000146648 (Ensembl)
EGR1GeneProductENSG00000120738 (Ensembl)
EPHA4GeneProductENSG00000116106 (Ensembl)
EPHNB2GeneProductENSG00000125266 (Ensembl)
FBRGeneProduct
FCGR2AGeneProductENSG00000143226 (Ensembl)
FECHP1GeneProductENSG00000235534 (Ensembl)
FK506Metabolite104987-11-3 (CAS)
FKBP1AGeneProductENSG00000088832 (Ensembl)
FOSGeneProductENSG00000170345 (Ensembl)
FOXO3GeneProductENSG00000118689 (Ensembl)
GADD45AGeneProductENSG00000116717 (Ensembl)
GAP43GeneProductENSG00000172020 (Ensembl)
GDNFGeneProductENSG00000168621 (Ensembl)
GFAPGeneProductENSG00000131095 (Ensembl)
GJA1GeneProductENSG00000152661 (Ensembl)
GRIN1GeneProductENSG00000176884 (Ensembl)
ICAM1GeneProductENSG00000090339 (Ensembl)
IFNGGeneProductENSG00000111537 (Ensembl)
IL1AGeneProduct3552 (Entrez Gene)
IL1BGeneProductENSG00000125538 (Ensembl)
IL1R1GeneProductENSG00000115594 (Ensembl)
IL2GeneProductENSG00000109471 (Ensembl)
IL4GeneProductENSG00000113520 (Ensembl)
IL6GeneProductENSG00000136244 (Ensembl)
KLK8GeneProductENSG00000129455 (Ensembl)
LEPGeneProductENSG00000174697 (Ensembl)
LGALS3GeneProductENSG00000131981 (Ensembl)
LILRB3GeneProductENSG00000204577 (Ensembl)
LTB4Metabolite169 (PubChem-compound)
LTB4RGeneProductENSG00000213903 (Ensembl)
LTBGeneProductENSG00000227507 (Ensembl)
MAGGeneProductENSG00000105695 (Ensembl)
MAPK1GeneProductENSG00000100030 (Ensembl)
MAPK3GeneProductENSG00000102882 (Ensembl)
MBPGeneProductENSG00000197971 (Ensembl)
MIFGeneProductENSG00000240972 (Ensembl)
MIR23BRnaENSG00000207563 (Ensembl)
MMP12GeneProductENSG00000262406 (Ensembl)
MMP9GeneProductENSG00000100985 (Ensembl)
MYCGeneProductENSG00000136997 (Ensembl)
NCANGeneProductENSG00000130287 (Ensembl)
NGFRGeneProductENSG00000064300 (Ensembl)
NOMetabolite145068 (PubChem-compound)
NOS1GeneProductENSG00000089250 (Ensembl)
NOS2GeneProductENSG00000007171 (Ensembl)
NOX4GeneProductENSG00000086991 (Ensembl)
NR4A1GeneProductENSG00000123358 (Ensembl)
NTN1GeneProductENSG00000065320 (Ensembl)
OMGGeneProductENSG00000126861 (Ensembl)
OlomoucineMetaboliteHMDB0035233 (HMDB)
PD 168393Metabolite4708 (PubChem-compound)
PDYNGeneProductENSG00000101327 (Ensembl)
PGH2MetaboliteHMDB0001381 (HMDB)
PLA2G2AGeneProductENSG00000188257 (Ensembl)
PLA2G5GeneProductENSG00000127472 (Ensembl)
PLA2G6GeneProductENSG00000184381 (Ensembl)
PLXNA2GeneProductENSG00000076356 (Ensembl)
PPP3CAGeneProductENSG00000138814 (Ensembl)
PRB1GeneProductENSG00000251655 (Ensembl)
PRKCAGeneProductENSG00000154229 (Ensembl)
PTGS2GeneProduct5743 (Entrez Gene)
PTPRAGeneProductENSG00000132670 (Ensembl)
PTPRZ1GeneProductENSG00000106278 (Ensembl)
RAC1GeneProductENSG00000136238 (Ensembl)
RB1GeneProductENSG00000139687 (Ensembl)
RGMAGeneProductENSG00000182175 (Ensembl)
RHOAGeneProductENSG00000067560 (Ensembl)
RHOBGeneProductENSG00000143878 (Ensembl)
RHOCGeneProductENSG00000155366 (Ensembl)
ROCK2GeneProductENSG00000134318 (Ensembl)
ROSGeneProduct6098 (Entrez Gene)
RTN4GeneProductENSG00000115310 (Ensembl)
RTN4RGeneProductENSG00000040608 (Ensembl)
SELPGeneProductENSG00000174175 (Ensembl)
SEMA6AGeneProductENSG00000092421 (Ensembl)
SLIT1GeneProductENSG00000187122 (Ensembl)
SLIT2GeneProductENSG00000145147 (Ensembl)
SLIT3GeneProductENSG00000184347 (Ensembl)
SOX9GeneProductENSG00000125398 (Ensembl)
TACR1GeneProductENSG00000115353 (Ensembl)
TGFB1GeneProductENSG00000105329 (Ensembl)
TLR4GeneProductENSG00000136869 (Ensembl)
TNFGeneProductENSG00000232810 (Ensembl)
TNFSF13BGeneProductENSG00000102524 (Ensembl)
TNFSF13GeneProductENSG00000161955 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl)
VCANGeneProductENSG00000038427 (Ensembl)
VIMGeneProductENSG00000026025 (Ensembl)
XYLT1GeneProductENSG00000103489 (Ensembl)
ZFP36GeneProductENSG00000128016 (Ensembl)
melittinMetabolite16133648 (PubChem-compound)