Effect of omega-3 PUFA on Huntington's disease pathways (Homo sapiens)

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510110886888696688966989881061899668381088184106863898918110108686698986912212111471Unknown connectionChloride influxLoss of cell potentialSubtype of GABAa receptor is unknownChloride influx Neuronal survivalLegendTranscription factorsApoptotic moleculesDownstreamkinasesGABRA1GABRB2PRKAG2GABRA6PRKAG1GABRDRapamycin PSPRKAB2EGFRGABRPGABRG2GABRG3GABRA3PRKAA2GABRQGABRA5PRKAB1GABRA4PRKAG3GABREGABRG1GABRB1GABRA2GABRB3PRKAA1GlutamateRAF1MSK1GRM1BDNFELK1CREBNTRK2EGFTrkBCASP3CASP7MAPK1RASHTTMAP2K1MAP2K2MAPK3DHARAB3AGTPRAB3AGDPRAB3GAP1EPADPANF-κB4GABAaRKCC2CKBGlutamateGlutamineCl-IL1BTNFIL6C1QAmHTTRESTKCC2KCC2KIF5HAP11Cl-NKCC11GABAaRCl-Cl-GABAaRGABAaRSP1GABA1111Cl-Cl-1Chloride efflux1Chloride effluxPI3KAKTHTTBDNFREST/NRSFNRSEmHTTSIN3AHDAC1HDAC2NRSEREST/NRSFBDNFBCL2 BAXBCL2L11BCL-xLBADBADBNIP3POPA1tBIDmHTTBIDCASP8HTTHAP1HAP1AHI1BDNFEGFRNEUROD1MLK2MAPKK7MAPKK4MAPKK4MAPKK7PPMAPK8MAPK9MAPK10ITPR1MTORMTORRAPTORDEPTORPRAS40MLST8RICTORPROTORDEPTORMLST8TSC1TSC2S6K1IKKβRHEBAMPKGTP4EBP1RHEBGDPTNF-AlphaEIF4ESubtype of AMPK is unknownmHTTDHAEPAPTEN8MAPK8MAPK9MAPK10EPAAKTAKT1AKT2AKT31111111111111111111111111111111111111111AstrocytesNeuronOligodendrocytesHMGCS1HMGCRHMGCS2MBPDHCR7PGC1amHTTABCG1CYP46A1LXRCholesterolSREBF2HMGCR24S-HCABCG4BDNFAPOECYP51A1ABCA1SREBF2LXRCholesterolmHTTABCA1ABCG1Cholesterol24S-HCCholesterolPGC1aPIK3CAPIK3CBPIK3CGPIK3CDClass 1 catalyticPIK3R1PIK3R2PIK3R3PIK3R4Class 1 regulatoryPIK3R5PIK3R6PIK3C2APIK3C2BPIK3C2GClass 2PIK3C2AClass 3PI3KHTTmHTTChloride effluxMutated Huntingtin geneWildtype Huntingtin gene


Description

This ERK pathway is implicated in Huntington's disease. The ligands BDNF, EGF, and Glu bind to their respective receptors (TrkB, EGFR, mGluR) and start a signal transduction pathway starting with RAS and RAF1, which leads to the stimulation of MEK then ERK. ERK promotes function of MSK1 (a downstream kinase), ElK1 and CREB (transcription factors), and caspases 3/7 (apoptotic molecules). These downstream targets are implicated in producing the effects of Huntington's disease at the cellular level. This pathway is based on Figure 1 from Bodai et al. Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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Bibliography

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  1. Hsu YT, Chang YG, Chern Y; ''Insights into GABA(A)ergic system alteration in Huntington's disease.''; Open Biol, 2018 PubMed Europe PMC Scholia
  2. Hong Y, Zhao T, Li XJ, Li S; ''Mutant Huntingtin Impairs BDNF Release from Astrocytes by Disrupting Conversion of Rab3a-GTP into Rab3a-GDP.''; J Neurosci, 2016 PubMed Europe PMC Scholia
  3. Dyall SC; ''Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA.''; Front Aging Neurosci, 2015 PubMed Europe PMC Scholia
  4. Jurcau A; ''Molecular Pathophysiological Mechanisms in Huntington's Disease.''; Biomedicines, 2022 PubMed Europe PMC Scholia
  5. Bodai L, Marsh JL; ''A novel target for Huntington's disease: ERK at the crossroads of signaling. The ERK signaling pathway is implicated in Huntington's disease and its upregulation ameliorates pathology.''; Bioessays, 2012 PubMed Europe PMC Scholia
  6. Sassone J, Maraschi A, Sassone F, Silani V, Ciammola A; ''Defining the role of the Bcl-2 family proteins in Huntington's disease.''; Cell Death Dis, 2013 PubMed Europe PMC Scholia
  7. Zuzana Paduchová, Barbora Katrenčíková, Magdaléna Vaváková, Lucia Laubertová, Zuzana Nagyová, Iveta Garaiova, Zdenka Ďuračková, Jana Trebatická; ''The Effect of Omega-3 Fatty Acids on Thromboxane, Brain-Derived Neurotrophic Factor, Homocysteine, and Vitamin D in Depressive Children and Adolescents: Randomized Controlled Trial''; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066966/, 2021 PubMed Europe PMC Scholia
  8. Shirooie S, Nabavi SF, Dehpour AR, Belwal T, Habtemariam S, Argüelles S, Sureda A, Daglia M, Tomczyk M, Sobarzo-Sanchez E, Xu S, Nabavi SM; ''Targeting mTORs by omega-3 fatty acids: A possible novel therapeutic strategy for neurodegeneration?''; Pharmacol Res, 2018 PubMed Europe PMC Scholia
  9. Wu LL, Zhou XF; ''Huntingtin associated protein 1 and its functions.''; Cell Adh Migr, 2009 PubMed Europe PMC Scholia
  10. Zuccato C, Tartari M, Crotti A, Goffredo D, Valenza M, Conti L, Cataudella T, Leavitt BR, Hayden MR, Timmusk T, Rigamonti D, Cattaneo E; ''Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes.''; Nat Genet, 2003 PubMed Europe PMC Scholia
  11. Leoni V, Caccia C; ''Study of cholesterol metabolism in Huntington's disease.''; Biochem Biophys Res Commun, 2014 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
134264view06:29, 19 July 2024EgonwFixed an Ensembl ID typo
134261view05:09, 18 July 2024EgonwRemoved redundant newlines
134218view09:06, 17 July 2024EgonwNormalized a data source name
129904view22:17, 23 May 2024EweitzOntology Term : 'neuron' added !
129903view22:17, 23 May 2024EweitzOntology Term : 'oligodendrocyte' added !
129902view22:17, 23 May 2024EweitzOntology Term : 'astrocyte' added !
129901view22:16, 23 May 2024EweitzEconomize layout
129895view21:59, 23 May 2024EweitzModified title
129783view09:57, 22 May 2024KimberleyBijl14 genes lacked identifiers
129782view09:48, 22 May 2024KimberleyBijlNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
24S-HC Metabolite34310 (ChEBI)
4EBP1GeneProductENSG00000187840 (Ensembl)
ABCA1GeneProductENSG00000165029 (Ensembl)
ABCG1GeneProductENSG00000160179 (Ensembl)
ABCG4GeneProductENSG00000172350 (Ensembl)
AHI1GeneProductENSG00000135541 (Ensembl) mutant Huntingtin
AKT1GeneProductENSG00000142208 (Ensembl)
AKT2GeneProductENSG00000105221 (Ensembl)
AKT3GeneProductENSG00000117020 (Ensembl)
AKTGeneProductENSG00000142208 (Ensembl)
AMPKGeneProductENSG00000132356 (Ensembl)
APOEGeneProductENSG00000130203 (Ensembl)
BADProteinENSG00000002330 (Ensembl)
BAXGeneProductENSG00000087088 (Ensembl)
BCL-xLGeneProductENSG00000171552 (Ensembl)
BCL2 GeneProductENSG00000171791 (Ensembl)
BCL2L11GeneProductENSG00000153094 (Ensembl)
BDNFGeneProductENSG00000176697 (Ensembl)
BIDGeneProductENSG00000015475 (Ensembl)
BNIP3GeneProductENSG00000176171 (Ensembl)
C1QAGeneProductENSG00000173372 (Ensembl)
CASP3GeneProductENSG00000164305 (Ensembl)
CASP7GeneProductENSG00000165806 (Ensembl)
CASP8GeneProductENSG00000064012 (Ensembl)
CKBGeneProductENSG00000166165 (Ensembl)
CREBGeneProductENSG00000118260 (Ensembl)
CYP46A1GeneProductENSG00000036530 (Ensembl)
CYP51A1GeneProductENSG00000001630 (Ensembl)
CholesterolMetabolite16113 (ChEBI)
Cl-Metabolite312 (PubChem-compound)
DEPTORGeneProductENSG00000155792 (Ensembl)
DHAMetaboliteLMFA01030185 (LIPID MAPS)
DHCR7GeneProductENSG00000172893 (Ensembl)
DPAMetabolite61204 (ChEBI)
EGFGeneProductENSG00000138798 (Ensembl)
EGFRGeneProductENSG00000146648 (Ensembl) mutant Huntingtin
EIF4EGeneProductENSG00000151247 (Ensembl)
ELK1GeneProductENSG00000126767 (Ensembl)
EPAMetabolite28364 (ChEBI)
GABAMetabolite16865 (ChEBI)
GABAaRGeneProductENSG00000022355 (Ensembl)
GABRA1GeneProductENSG00000022355 (Ensembl)
GABRA2GeneProductENSG00000151834 (Ensembl)
GABRA3GeneProductENSG00000011677 (Ensembl)
GABRA4GeneProductENSG00000109158 (Ensembl)
GABRA5GeneProductENSG00000186297 (Ensembl)
GABRA6GeneProductENSG00000145863 (Ensembl)
GABRB1GeneProductENSG00000163288 (Ensembl)
GABRB2GeneProductENSG00000145864 (Ensembl)
GABRB3GeneProductENSG00000166206 (Ensembl)
GABRDGeneProductENSG00000187730 (Ensembl)
GABREGeneProductENSG00000102287 (Ensembl)
GABRG1GeneProductENSG00000163285 (Ensembl)
GABRG2GeneProductENSG00000113327 (Ensembl)
GABRG3GeneProductENSG00000182256 (Ensembl)
GABRPGeneProductENSG00000094755 (Ensembl)
GABRQGeneProductENSG00000268089 (Ensembl)
GRM1GeneProductENSG00000152822 (Ensembl)
GlutamateMetabolite14321 (ChEBI)
GlutamineMetabolite18050 (ChEBI)
HAP1GeneProductENSG00000173805 (Ensembl) mutant Huntingtin
HDAC1GeneProductENSG00000116478 (Ensembl)
HDAC2GeneProductENSG00000196591 (Ensembl)
HMGCRGeneProductENSG00000113161 (Ensembl)
HMGCS1GeneProductENSG00000112972 (Ensembl)
HMGCS2GeneProductENSG00000134240 (Ensembl)
HTTGeneProductENSG00000197386 (Ensembl) mutant Huntingtin
IKKβGeneProductENSG00000104365 (Ensembl)
IL1BGeneProductENSG00000125538 (Ensembl)
IL6GeneProductENSG00000136244 (Ensembl)
ITPR1GeneProductENSG00000150995 (Ensembl) mutant Huntingtin
KCC2GeneProductENSG00000124140 (Ensembl)
KIF5GeneProductENSG00000155980 (Ensembl)
LXR ProteinP55055 (Uniprot-TrEMBL)
MAP2K1GeneProductENSG00000169032 (Ensembl)
MAP2K2GeneProductENSG00000126934 (Ensembl)
MAPK10GeneProductENSG00000109339 (Ensembl) mutant Huntingtin
MAPK1GeneProductENSG00000100030 (Ensembl)
MAPK3GeneProductENSG00000102882 (Ensembl)
MAPK8GeneProductENSG00000107643 (Ensembl) mutant Huntingtin
MAPK9GeneProductENSG00000050748 (Ensembl) mutant Huntingtin
MAPKK4GeneProductENSG00000065559 (Ensembl) mutant Huntingtin
MAPKK7GeneProductENSG00000076984 (Ensembl) mutant Huntingtin
MBPGeneProductENSG00000197971 (Ensembl)
MLK2 GeneProductENSG00000130758 (Ensembl) mutant Huntingtin
MLST8GeneProductENSG00000167965 (Ensembl)
MSK1GeneProductENSG00000100784 (Ensembl)
MTORGeneProductENSG00000198793 (Ensembl)
NEUROD1GeneProductENSG00000162992 (Ensembl) mutant Huntingtin
NF-κBProteinENSG00000109320 (Ensembl) mutant Huntingtin
NKCC1GeneProductENSG00000064651 (Ensembl)
NRSEGeneProductENSG00000084093 (Ensembl)
NTRK2GeneProductENSG00000148053 (Ensembl)
OPA1GeneProductENSG00000198836 (Ensembl)
PGC1aProteinENSG00000109819 (Ensembl)
PI3KGeneProductENSG00000124102 (Ensembl)
PIK3C2AGeneProductENSG00000011405 (Ensembl)
PIK3C2BGeneProductENSG00000133056 (Ensembl)
PIK3C2GGeneProductENSG00000139144 (Ensembl)
PIK3CAGeneProductENSG00000121879 (Ensembl)
PIK3CBGeneProductENSG00000051382 (Ensembl)
PIK3CDGeneProductENSG00000171608 (Ensembl)
PIK3CGGeneProductENSG00000105851 (Ensembl)
PIK3R1GeneProductENSG00000145675 (Ensembl)
PIK3R2GeneProductENSG00000105647 (Ensembl)
PIK3R3GeneProductENSG00000117461 (Ensembl)
PIK3R4GeneProductENSG00000196455 (Ensembl)
PIK3R5GeneProductENSG00000141506 (Ensembl)
PIK3R6GeneProductENSG00000276231 (Ensembl)
PRAS40GeneProductENSG00000204673 (Ensembl)
PRKAA1GeneProductENSG00000132356 (Ensembl)
PRKAA2GeneProductENSG00000162409 (Ensembl)
PRKAB1GeneProductENG00000111725 (Ensembl)
PRKAB2GeneProductENSG00000131791 (Ensembl)
PRKAG1GeneProductENSG00000181929 (Ensembl)
PRKAG2GeneProductENSG00000106617 (Ensembl)
PRKAG3GeneProductENSG00000115592 (Ensembl)
PROTORGeneProductENSG00000135362 (Ensembl)
PSMetabolite18303 (ChEBI)
PTENGeneProductENSG00000171862 (Ensembl)
RAB3AGeneProductENSG00000105649 (Ensembl) mutant Huntingtin
RAB3GAP1GeneProductENSG00000115839 (Ensembl) mutant Huntingtin
RAF1GeneProductENSG00000132155 (Ensembl)
RAPTORGeneProductENSG00000141564 (Ensembl)
RASGeneProductENSG00000174775 (Ensembl)
REST/NRSFGeneProductENSG00000084093 (Ensembl)
RESTGeneProductENSG00000084093 (Ensembl)
RHEBGeneProductENSG00000106615 (Ensembl)
RICTORGeneProductENSG00000164327 (Ensembl)
Rapamycin Metabolite5497196 (PubChem-compound)
S6K1 GeneProductENSG00000108443 (Ensembl)
SIN3AGeneProductENSG00000169375 (Ensembl)
SP1GeneProductENSG00000185591 (Ensembl) mutant Huntingtin
SREBF2GeneProductENSG00000198911 (Ensembl)
TNF-AlphaGeneProductENSG00000228978 (Ensembl)
TNFGeneProductENSG00000228978 (Ensembl)
TSC1GeneProductENSG00000165699 (Ensembl)
TSC2GeneProductENSG00000103197 (Ensembl)
TrkBProteinENSG00000148053 (Ensembl Human)
mHTTGeneProductENSG00000197386 (Ensembl) mutant Huntingtin
tBIDGeneProductENSG00000015475 (Ensembl)

Annotated Interactions

No annotated interactions

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