Crosstalk between the UPR and autophagy pathway contributes to handling cellular stress in neurodegenerative disease

Figure 1. Signaling crosstalk between the UPR and autophagy in the nervous system. mHTT pathogenesis triggers ER stress, engaging UPR stress sensors. Activated ERN1/IRE1 induces the TRAF2-MAPK8 pathway, inducing autophagy independent of XBP1. PERK activation and phosphorylation of EIF2S1/eIF2α, leads to upregulation of ATG12 possibly through the transcriptional activity of ATF4. XBP1 negatively regulates the levels of FOXO1, inducing its degradation by the proteasome. Then, inactivation of XBP1 protects against HD due to increased accumulation of FOXO1 and the upregulation of its target genes, which include many autophagy regulators. Signaling events related with aging (i.e., insulin and IGF1 signaling) may intersect in FOXO1 and XBP1 to modulate autophagy levels in HD.
Crosstalk between the UPR and autophagy pathway contributes to handling cellular stress in neurodegenerative disease
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Crosstalk between the UPR and autophagy pathway contributes to handling cellular stress in neurodegenerative disease. (2012) René L. Vidal, et al. Autophagy. 2012 Jun 1;8(6):970-972. Figure: F1.

Gene mentions


Organism Group Word Match Source NCBI Symbol NCBI ID
Homo sapiens Primates ATG12,ATG5,LC3,BECN1 BECN1 ncbigene_symbol BECN1 8678
Homo sapiens Primates ATG12,ATG5,LC3,BECN1 ATG12 ncbigene_symbol ATG12 9140
Homo sapiens Primates ATG12,ATG5,LC3,BECN1 LC3 ncbigene_synonym MAP1LC3A 84557
Homo sapiens Primates ATG12,ATG5,LC3,BECN1 ATG5 ncbigene_symbol ATG5 9474
Homo sapiens Primates ATF4 ATF4 ncbigene_symbol ATF4 468
Homo sapiens Primates (elF2a) EIF2A ncbigene_symbol EIF2A 83939
Homo sapiens Primates (elF2a) EIF2A ncbigene_synonym EIF2S1 1965
Homo sapiens Primates PERK PERK ncbigene_synonym EIF2AK3 9451
Homo sapiens Primates JNK JNK ncbigene_synonym MAPK8 5599
Homo sapiens Primates JNK JNK famplex_relations MAPK9 5601
Homo sapiens Primates JNK JNK famplex_relations MAPK10 5602
Homo sapiens Primates (BCL2, BCL2 ncbigene_symbol BCL2 596
Homo sapiens Primates (TRAF2 TRAF2 ncbigene_symbol TRAF2 7186
Homo sapiens Primates (TRAF2 TRAF2 ncbigene_synonym TANK 10010
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMA1 5682
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMA2 5683
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMA3 5684
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMA4 5685
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMA5 5686
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMA6 5687
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMA7 5688
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMA8 143471
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMB1 5689
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMB10 5699
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMB2 5690
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMB3 5691
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMB4 5692
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMB5 5693
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMB6 5694
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMB7 5695
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMB8 5696
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMB9 5698
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMC1 5700
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMC2 5701
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMC3 5702
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMC4 5704
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMC5 5705
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMC6 5706
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMD1 5707
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMD10 5716
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMD11 5717
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMD12 5718
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMD13 5719
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMD14 10213
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMD2 5708
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMD3 5709
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMD4 5710
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMD5 5711
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMD6 9861
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMD7 5713
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMD8 5714
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMD9 5715
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSME1 5720
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSME2 5721
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSME3 10197
Homo sapiens Primates Proteasome PROTEASOME famplex_relations PSMF1 9491
Homo sapiens Primates Proteasome PROTEASOME famplex_relations SEM1 7979
Homo sapiens Primates Proteasome PROTEASOME famplex_relations USP5 8078
Homo sapiens Primates IRE1 IRE1 ncbigene_synonym ERN1 2081
Homo sapiens Primates FOXO1 FOXO1 ncbigene_symbol FOXO1 2308
Homo sapiens Primates pta PTA ncbigene_synonym F11 2160
Homo sapiens Primates pta PTA ncbigene_synonym PTCRA 171558
Homo sapiens Primates IGF1 IGF1 ncbigene_symbol IGF1 3479
Homo sapiens Primates Irs2 IRS2 ncbigene_symbol IRS2 8660
Mus musculus Rodents ATG12,ATG5,LC3,BECN1 BECN1 ncbigene_symbol Becn1 56208
Mus musculus Rodents ATG12,ATG5,LC3,BECN1 ATG12 ncbigene_symbol Atg12 67526
Mus musculus Rodents ATG12,ATG5,LC3,BECN1 LC3 ncbigene_synonym Map1lc3a 66734
Mus musculus Rodents ATG12,ATG5,LC3,BECN1 ATG5 ncbigene_symbol Atg5 11793
Mus musculus Rodents ATF4 ATF4 ncbigene_symbol Atf4 11911
Mus musculus Rodents (elF2a) EIF2A ncbigene_symbol Eif2a 229317
Mus musculus Rodents (elF2a) EIF2A ncbigene_synonym Eif2s1 13665
Mus musculus Rodents PERK PERK ncbigene_synonym Eif2ak3 13666
Mus musculus Rodents PERK PERK ncbigene_synonym Lamp1 16783
Mus musculus Rodents JNK JNK ncbigene_synonym Mapk8 26419
Mus musculus Rodents (BCL2, BCL2 ncbigene_symbol Bcl2 12043
Mus musculus Rodents (TRAF2 TRAF2 ncbigene_symbol Traf2 22030
Mus musculus Rodents IRE1 IRE1 ncbigene_synonym Ern2 26918
Mus musculus Rodents FOXO1 FOXO1 ncbigene_symbol Foxo1 56458
Mus musculus Rodents pta PTA ncbigene_synonym Ptcra 19208
Mus musculus Rodents pta PTA ncbigene_synonym F11 109821
Mus musculus Rodents IGF1 IGF1 ncbigene_symbol Igf1 16000
Mus musculus Rodents Irs2 IRS2 ncbigene_symbol Irs2 384783
Danio rerio Vertebrates ATG12,ATG5,LC3,BECN1 BECN1 ncbigene_symbol becn1 393846
Danio rerio Vertebrates ATG12,ATG5,LC3,BECN1 ATG12 ncbigene_symbol atg12 570965
Danio rerio Vertebrates ATG12,ATG5,LC3,BECN1 LC3 ncbigene_synonym b3gnt5a 336526
Danio rerio Vertebrates ATG12,ATG5,LC3,BECN1 ATG5 ncbigene_symbol atg5 494180
Danio rerio Vertebrates ATF4 ATF4 ncbigene_synonym atf4a 406514
Danio rerio Vertebrates (elF2a) ELF2A ncbigene_symbol elf2a 445489
Danio rerio Vertebrates (elF2a) EIF2A ncbigene_symbol eif2a 573991
Danio rerio Vertebrates JNK JNK ncbigene_synonym mapk8b 65236
Danio rerio Vertebrates (BCL2, BCL2 ncbigene_synonym bcl2a 570772
Danio rerio Vertebrates FOXO1 FOXO1 ncbigene_synonym foxo1a 768121
Danio rerio Vertebrates IGF1 IGF1 ncbigene_symbol igf1 114433
Danio rerio Vertebrates Irs2 IRS2 ncbigene_synonym irs2b 572001

Chemical mentions

Word Match MeSH Name ChEBI

Disease mentions

Word Match MeSH Name DOID