KEGG   PATHWAY: hsa05014
Entry
hsa05014                    Pathway                                

Name
Amyotrophic lateral sclerosis - Homo sapiens (human)
Description
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by a progressive degeneration of motor neurons in the brain and spinal cord. In 90% of patients, ALS is sporadic, with no clear genetic linkage. On the other hand, the remaining 10% of cases show familial inheritance, with mutations in SOD1, TDP43(TARDBP), FUS, or C9orf72 genes being the most frequent causes. In spite of such difference, familial ALS and sporadic ALS have similarities in their pathological features. Proposed disease mechanisms contributing to motor neuron degeneration in ALS are: impaired proteostasis, aberrant RNA processing, mitochondrial disfunction and oxidative stress, microglia activation, and axonal dysfunction.
Class
Human Diseases; Neurodegenerative disease
Pathway map
hsa05014  Amyotrophic lateral sclerosis
hsa05014

Network
nt06410  Calcium signaling
nt06412  Unfolded protein response (UPR) signaling
nt06413  Autophagy
nt06414  Apoptosis
nt06415  PI3K signaling
nt06418  Oxidative phosphorylation
nt06419  Microtubule-based transport
nt06420  Ubiquitin-proteasome system
nt06421  Mitophagy
nt06423  Cytoskeletal regulation
nt06424  RNA processing
nt06464  Amyotrophic lateral sclerosis
  Element
N01135  Mutation-caused aberrant SOD1 to intrinsic apoptotic pathway
N01136  Mutation-caused aberrant TDP43 to electron transfer in Complex I
N01138  Mutation-inactivated OPTN to PINK-Parkin-mediated autophagosome formation
N01139  Mutation-inactivated p62 to PINK-Parkin-mediated autophagosome formation
N01141  Mutation-inactivated TBK1 to TBK1-mediated autophagosome formation
N01143  Mutation-inactivated C9orf72 to C9orf72-mediated autophagy initiation
N01144  Mutation-caused aberrant SOD1 to 26S proteasome-mediated protein degradation
N01145  Mutation-inactivated VCP to 26S proteasome-mediated protein degradation
N01146  Mutation-inactivated UBQLN2 to 26S proteasome-mediated protein degradation
N01147  Mutation-caused aberrant SOD1 to ATF6-mediated transcription
N01148  Mutation-caused aberrant SOD1 to IRE1a-XBP1 signaling pathway
N01149  Mutation-caused aberrant SOD1 to PERK-ATF4 signaling pathway
N01150  Mutation-inactivated VAPB to ATF6-mediated transcription
N01151  Mutation-inactivated SIGMAR1 to Ca2+ -apoptotic pathway
N01153  Mutation-caused aberrant GLE1 to nuclear export of mRNA
N01155  Mutation-caused aberrant TDP43 to TDP-43-regulated splicing
N01157  Mutation-caused aberrant FUS to FUS-regulated splicing
N01158  Mutation-caused aberrant DCTN1 to retrograde axonal transport
N01159  Mutation-caused aberrant TUBA4A to retrograde axonal transport
N01160  Mutation-caused aberrant SOD1 to retrograde axonal transport
N01162  Mutation-caused aberrant PFN1 to actin polymerization
N01164  Mutation-inactivated ERBB4 to NRG-ERBB4-PI3K signaling pathway
Disease
H00058  Amyotrophic lateral sclerosis (ALS)
H00970  Juvenile primary lateral sclerosis
Drug
D00775  Riluzole (JAN/USP/INN)
D10416  Belnacasan (USAN)
D11811  Tofersen (JAN/USAN/INN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
7157  TP53; tumor protein p53 [KO:K04451]
834  CASP1; caspase 1 [KO:K01370] [EC:3.4.22.36]
637  BID; BH3 interacting domain death agonist [KO:K04726]
596  BCL2; BCL2 apoptosis regulator [KO:K02161]
598  BCL2L1; BCL2 like 1 [KO:K04570]
581  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
572  BAD; BCL2 associated agonist of cell death [KO:K02158]
317  APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
54205  CYCS; cytochrome c, somatic [KO:K08738]
842  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
836  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
6647  SOD1; superoxide dismutase 1 [KO:K04565] [EC:1.15.1.1]
4535  ND1; NADH dehydrogenase subunit 1 [KO:K03878] [EC:7.1.1.2]
4536  ND2; NADH dehydrogenase subunit 2 [KO:K03879] [EC:7.1.1.2]
4537  ND3; NADH dehydrogenase subunit 3 [KO:K03880] [EC:7.1.1.2]
4538  ND4; NADH dehydrogenase subunit 4 [KO:K03881] [EC:7.1.1.2]
4539  ND4L; NADH dehydrogenase subunit 4L [KO:K03882] [EC:7.1.1.2]
4540  ND5; NADH dehydrogenase subunit 5 [KO:K03883] [EC:7.1.1.2]
4541  ND6; NADH dehydrogenase subunit 6 [KO:K03884] [EC:7.1.1.2]
4723  NDUFV1; NADH:ubiquinone oxidoreductase core subunit V1 [KO:K03942] [EC:7.1.1.2]
4729  NDUFV2; NADH:ubiquinone oxidoreductase core subunit V2 [KO:K03943] [EC:7.1.1.2]
4731  NDUFV3; NADH:ubiquinone oxidoreductase subunit V3 [KO:K03944]
4694  NDUFA1; NADH:ubiquinone oxidoreductase subunit A1 [KO:K03945]
4695  NDUFA2; NADH:ubiquinone oxidoreductase subunit A2 [KO:K03946]
4696  NDUFA3; NADH:ubiquinone oxidoreductase subunit A3 [KO:K03947]
4697  NDUFA4; NDUFA4 mitochondrial complex associated [KO:K03948]
56901  NDUFA4L2; NDUFA4 mitochondrial complex associated like 2 [KO:K03948]
4698  NDUFA5; NADH:ubiquinone oxidoreductase subunit A5 [KO:K03949]
4700  NDUFA6; NADH:ubiquinone oxidoreductase subunit A6 [KO:K03950]
4701  NDUFA7; NADH:ubiquinone oxidoreductase subunit A7 [KO:K03951]
4702  NDUFA8; NADH:ubiquinone oxidoreductase subunit A8 [KO:K03952]
4704  NDUFA9; NADH:ubiquinone oxidoreductase subunit A9 [KO:K03953]
4705  NDUFA10; NADH:ubiquinone oxidoreductase subunit A10 [KO:K03954]
4706  NDUFAB1; NADH:ubiquinone oxidoreductase subunit AB1 [KO:K03955]
126328  NDUFA11; NADH:ubiquinone oxidoreductase subunit A11 [KO:K03956]
55967  NDUFA12; NADH:ubiquinone oxidoreductase subunit A12 [KO:K11352]
51079  NDUFA13; NADH:ubiquinone oxidoreductase subunit A13 [KO:K11353]
4707  NDUFB1; NADH:ubiquinone oxidoreductase subunit B1 [KO:K03957]
4708  NDUFB2; NADH:ubiquinone oxidoreductase subunit B2 [KO:K03958]
4709  NDUFB3; NADH:ubiquinone oxidoreductase subunit B3 [KO:K03959]
4710  NDUFB4; NADH:ubiquinone oxidoreductase subunit B4 [KO:K03960]
4711  NDUFB5; NADH:ubiquinone oxidoreductase subunit B5 [KO:K03961]
4712  NDUFB6; NADH:ubiquinone oxidoreductase subunit B6 [KO:K03962]
4713  NDUFB7; NADH:ubiquinone oxidoreductase subunit B7 [KO:K03963]
4714  NDUFB8; NADH:ubiquinone oxidoreductase subunit B8 [KO:K03964]
4715  NDUFB9; NADH:ubiquinone oxidoreductase subunit B9 [KO:K03965]
4716  NDUFB10; NADH:ubiquinone oxidoreductase subunit B10 [KO:K03966]
54539  NDUFB11; NADH:ubiquinone oxidoreductase subunit B11 [KO:K11351]
4719  NDUFS1; NADH:ubiquinone oxidoreductase core subunit S1 [KO:K03934] [EC:7.1.1.2]
4720  NDUFS2; NADH:ubiquinone oxidoreductase core subunit S2 [KO:K03935] [EC:7.1.1.2]
4722  NDUFS3; NADH:ubiquinone oxidoreductase core subunit S3 [KO:K03936] [EC:7.1.1.2]
4724  NDUFS4; NADH:ubiquinone oxidoreductase subunit S4 [KO:K03937]
4725  NDUFS5; NADH:ubiquinone oxidoreductase subunit S5 [KO:K03938]
4726  NDUFS6; NADH:ubiquinone oxidoreductase subunit S6 [KO:K03939]
374291  NDUFS7; NADH:ubiquinone oxidoreductase core subunit S7 [KO:K03940] [EC:7.1.1.2]
4728  NDUFS8; NADH:ubiquinone oxidoreductase core subunit S8 [KO:K03941] [EC:7.1.1.2]
4717  NDUFC1; NADH:ubiquinone oxidoreductase subunit C1 [KO:K03967]
4718  NDUFC2; NADH:ubiquinone oxidoreductase subunit C2 [KO:K03968]
100532726  NDUFC2-KCTD14; NDUFC2-KCTD14 readthrough [KO:K03968]
6389  SDHA; succinate dehydrogenase complex flavoprotein subunit A [KO:K00234] [EC:1.3.5.1]
6390  SDHB; succinate dehydrogenase complex iron sulfur subunit B [KO:K00235] [EC:1.3.5.1]
6391  SDHC; succinate dehydrogenase complex subunit C [KO:K00236]
6392  SDHD; succinate dehydrogenase complex subunit D [KO:K00237]
7386  UQCRFS1; ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 [KO:K00411] [EC:7.1.1.8]
4519  CYTB; cytochrome b [KO:K00412]
1537  CYC1; cytochrome c1 [KO:K00413]
7384  UQCRC1; ubiquinol-cytochrome c reductase core protein 1 [KO:K00414]
7385  UQCRC2; ubiquinol-cytochrome c reductase core protein 2 [KO:K00415]
7388  UQCRH; ubiquinol-cytochrome c reductase hinge protein [KO:K00416]
440567  UQCRHL; ubiquinol-cytochrome c reductase hinge protein like [KO:K00416]
7381  UQCRB; ubiquinol-cytochrome c reductase binding protein [KO:K00417]
27089  UQCRQ; ubiquinol-cytochrome c reductase complex III subunit VII [KO:K00418]
29796  UQCR10; ubiquinol-cytochrome c reductase, complex III subunit X [KO:K00419]
10975  UQCR11; ubiquinol-cytochrome c reductase, complex III subunit XI [KO:K00420]
4514  COX3; cytochrome c oxidase subunit III [KO:K02262]
4512  COX1; cytochrome c oxidase subunit I [KO:K02256] [EC:7.1.1.9]
4513  COX2; cytochrome c oxidase subunit II [KO:K02261]
84701  COX4I2; cytochrome c oxidase subunit 4I2 [KO:K02263]
1327  COX4I1; cytochrome c oxidase subunit 4I1 [KO:K02263]
9377  COX5A; cytochrome c oxidase subunit 5A [KO:K02264]
1329  COX5B; cytochrome c oxidase subunit 5B [KO:K02265]
1337  COX6A1; cytochrome c oxidase subunit 6A1 [KO:K02266]
1339  COX6A2; cytochrome c oxidase subunit 6A2 [KO:K02266]
1340  COX6B1; cytochrome c oxidase subunit 6B1 [KO:K02267]
125965  COX6B2; cytochrome c oxidase subunit 6B2 [KO:K02267]
1345  COX6C; cytochrome c oxidase subunit 6C [KO:K02268]
1346  COX7A1; cytochrome c oxidase subunit 7A1 [KO:K02270]
1347  COX7A2; cytochrome c oxidase subunit 7A2 [KO:K02270]
9167  COX7A2L; cytochrome c oxidase subunit 7A2 like [KO:K02270]
1349  COX7B; cytochrome c oxidase subunit 7B [KO:K02271]
170712  COX7B2; cytochrome c oxidase subunit 7B2 [KO:K02271]
1350  COX7C; cytochrome c oxidase subunit 7C [KO:K02272]
341947  COX8C; cytochrome c oxidase subunit 8C [KO:K02273]
1351  COX8A; cytochrome c oxidase subunit 8A [KO:K02273]
498  ATP5F1A; ATP synthase F1 subunit alpha [KO:K02132]
506  ATP5F1B; ATP synthase F1 subunit beta [KO:K02133] [EC:7.1.2.2]
509  ATP5F1C; ATP synthase F1 subunit gamma [KO:K02136]
513  ATP5F1D; ATP synthase F1 subunit delta [KO:K02134]
514  ATP5F1E; ATP synthase F1 subunit epsilon [KO:K02135]
4508  ATP6; ATP synthase F0 subunit 6 [KO:K02126]
515  ATP5PB; ATP synthase peripheral stalk-membrane subunit b [KO:K02127]
516  ATP5MC1; ATP synthase membrane subunit c locus 1 [KO:K02128]
517  ATP5MC2; ATP synthase membrane subunit c locus 2 [KO:K02128]
518  ATP5MC3; ATP synthase membrane subunit c locus 3 [KO:K02128]
10476  ATP5PD; ATP synthase peripheral stalk subunit d [KO:K02138]
539  ATP5PO; ATP synthase peripheral stalk subunit OSCP [KO:K02137]
522  ATP5PF; ATP synthase peripheral stalk subunit F6 [KO:K02131]
4509  ATP8; ATP synthase F0 subunit 8 [KO:K02125]
7416  VDAC1; voltage dependent anion channel 1 [KO:K05862]
10452  TOMM40; translocase of outer mitochondrial membrane 40 [KO:K11518]
84134  TOMM40L; translocase of outer mitochondrial membrane 40 like [KO:K11518]
90550  MCU; mitochondrial calcium uniporter [KO:K20858]
65018  PINK1; PTEN induced kinase 1 [KO:K05688] [EC:2.7.11.1]
5071  PRKN; parkin RBR E3 ubiquitin protein ligase [KO:K04556] [EC:2.3.2.31]
10133  OPTN; optineurin [KO:K19946]
8878  SQSTM1; sequestosome 1 [KO:K14381]
11337  GABARAP; GABA type A receptor-associated protein [KO:K08341]
23710  GABARAPL1; GABA type A receptor associated protein like 1 [KO:K08341]
11345  GABARAPL2; GABA type A receptor associated protein like 2 [KO:K08341]
29110  TBK1; TANK binding kinase 1 [KO:K05410] [EC:2.7.11.10]
10010  TANK; TRAF family member associated NFKB activator [KO:K12650]
55255  WDR41; WD repeat domain 41 [KO:K23610]
140775  SMCR8; SMCR8-C9orf72 complex subunit [KO:K23611]
203228  C9orf72; C9orf72-SMCR8 complex subunit [KO:K23609]
4218  RAB8A; RAB8A, member RAS oncogene family [KO:K07901]
116442  RAB39B; RAB39B, member RAS oncogene family [KO:K07925]
5861  RAB1A; RAB1A, member RAS oncogene family [KO:K07874]
2475  MTOR; mechanistic target of rapamycin kinase [KO:K07203] [EC:2.7.11.1]
8408  ULK1; unc-51 like autophagy activating kinase 1 [KO:K21357] [EC:2.7.11.1]
9706  ULK2; unc-51 like autophagy activating kinase 2 [KO:K08269] [EC:2.7.11.1]
60673  ATG101; autophagy related 101 [KO:K19730]
9776  ATG13; autophagy related 13 [KO:K08331]
9821  RB1CC1; RB1 inducible coiled-coil 1 [KO:K17589]
55626  AMBRA1; autophagy and beclin 1 regulator 1 [KO:K17985]
8678  BECN1; beclin 1 [KO:K08334]
441925  BECN2; beclin 2 [KO:K08334]
30849  PIK3R4; phosphoinositide-3-kinase regulatory subunit 4 [KO:K08333] [EC:2.7.11.1]
22863  ATG14; autophagy related 14 [KO:K17889]
29982  NRBF2; nuclear receptor binding factor 2 [KO:K21246]
5289  PIK3C3; phosphatidylinositol 3-kinase catalytic subunit type 3 [KO:K00914] [EC:2.7.1.137]
23130  ATG2A; autophagy related 2A [KO:K17906]
55102  ATG2B; autophagy related 2B [KO:K17906]
26100  WIPI2; WD repeat domain, phosphoinositide interacting 2 [KO:K17908]
55062  WIPI1; WD repeat domain, phosphoinositide interacting 1 [KO:K17908]
57679  ALS2; alsin Rho guanine nucleotide exchange factor ALS2 [KO:K04575]
5868  RAB5A; RAB5A, member RAS oncogene family [KO:K07887]
5879  RAC1; Rac family small GTPase 1 [KO:K04392]
25978  CHMP2B; charged multivesicular body protein 2B [KO:K12192]
9896  FIG4; FIG4 phosphoinositide 5-phosphatase [KO:K22913] [EC:3.1.3.-]
80208  SPG11; SPG11 vesicle trafficking associated, spatacsin [KO:K19026]
5530  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
5532  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
5533  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
5534  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
5535  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
29979  UBQLN1; ubiquilin 1 [KO:K04523]
29978  UBQLN2; ubiquilin 2 [KO:K04523]
50613  UBQLN3; ubiquilin 3 [KO:K04523]
56893  UBQLN4; ubiquilin 4 [KO:K04523]
7415  VCP; valosin containing protein [KO:K13525]
79139  DERL1; derlin 1 [KO:K11519]
5687  PSMA6; proteasome 20S subunit alpha 6 [KO:K02730] [EC:3.4.25.1]
5683  PSMA2; proteasome 20S subunit alpha 2 [KO:K02726] [EC:3.4.25.1]
5685  PSMA4; proteasome 20S subunit alpha 4 [KO:K02728] [EC:3.4.25.1]
5688  PSMA7; proteasome 20S subunit alpha 7 [KO:K02731] [EC:3.4.25.1]
143471  PSMA8; proteasome 20S subunit alpha 8 [KO:K02731] [EC:3.4.25.1]
5686  PSMA5; proteasome 20S subunit alpha 5 [KO:K02729] [EC:3.4.25.1]
5682  PSMA1; proteasome 20S subunit alpha 1 [KO:K02725] [EC:3.4.25.1]
5684  PSMA3; proteasome 20S subunit alpha 3 [KO:K02727] [EC:3.4.25.1]
5694  PSMB6; proteasome 20S subunit beta 6 [KO:K02738] [EC:3.4.25.1]
5695  PSMB7; proteasome 20S subunit beta 7 [KO:K02739] [EC:3.4.25.1]
5691  PSMB3; proteasome 20S subunit beta 3 [KO:K02735] [EC:3.4.25.1]
5690  PSMB2; proteasome 20S subunit beta 2 [KO:K02734] [EC:3.4.25.1]
5693  PSMB5; proteasome 20S subunit beta 5 [KO:K02737] [EC:3.4.25.1]
5689  PSMB1; proteasome 20S subunit beta 1 [KO:K02732] [EC:3.4.25.1]
5692  PSMB4; proteasome 20S subunit beta 4 [KO:K02736] [EC:3.4.25.1]
5701  PSMC2; proteasome 26S subunit, ATPase 2 [KO:K03061]
5700  PSMC1; proteasome 26S subunit, ATPase 1 [KO:K03062]
5704  PSMC4; proteasome 26S subunit, ATPase 4 [KO:K03063]
5706  PSMC6; proteasome 26S subunit, ATPase 6 [KO:K03064]
5702  PSMC3; proteasome 26S subunit, ATPase 3 [KO:K03065]
5705  PSMC5; proteasome 26S subunit, ATPase 5 [KO:K03066]
5708  PSMD2; proteasome 26S subunit ubiquitin receptor, non-ATPase 2 [KO:K03028]
5707  PSMD1; proteasome 26S subunit, non-ATPase 1 [KO:K03032]
5709  PSMD3; proteasome 26S subunit, non-ATPase 3 [KO:K03033]
5715  PSMD9; proteasome 26S subunit, non-ATPase 9 [KO:K06693]
5718  PSMD12; proteasome 26S subunit, non-ATPase 12 [KO:K03035]
5717  PSMD11; proteasome 26S subunit, non-ATPase 11 [KO:K03036]
9861  PSMD6; proteasome 26S subunit, non-ATPase 6 [KO:K03037]
5713  PSMD7; proteasome 26S subunit, non-ATPase 7 [KO:K03038]
5719  PSMD13; proteasome 26S subunit, non-ATPase 13 [KO:K03039]
5710  PSMD4; proteasome 26S subunit ubiquitin receptor, non-ATPase 4 [KO:K03029]
10213  PSMD14; proteasome 26S subunit, non-ATPase 14 [KO:K03030]
5714  PSMD8; proteasome 26S subunit, non-ATPase 8 [KO:K03031]
11047  ADRM1; ADRM1 26S proteasome ubiquitin receptor [KO:K06691]
7979  SEM1; SEM1 26S proteasome subunit [KO:K10881]
10013  HDAC6; histone deacetylase 6 [KO:K11407] [EC:3.5.1.98]
23435  TARDBP; TAR DNA binding protein [KO:K23600]
2521  FUS; FUS RNA binding protein [KO:K13098]
220988  HNRNPA3; heterogeneous nuclear ribonucleoprotein A3 [KO:K12741]
3178  HNRNPA1; heterogeneous nuclear ribonucleoprotein A1 [KO:K12741]
144983  HNRNPA1L2; heterogeneous nuclear ribonucleoprotein A1 like 2 [KO:K12741]
3181  HNRNPA2B1; heterogeneous nuclear ribonucleoprotein A2/B1 [KO:K13158]
11273  ATXN2L; ataxin 2 like [KO:K23625]
6311  ATXN2; ataxin 2 [KO:K23625]
9782  MATR3; matrin 3 [KO:K13213]
283  ANG; angiogenin [KO:K16631] [EC:3.1.27.-]
4686  NCBP1; nuclear cap binding protein subunit 1 [KO:K12882]
10189  ALYREF; Aly/REF export factor [KO:K12881]
6428  SRSF3; serine and arginine rich splicing factor 3 [KO:K12892]
6432  SRSF7; serine and arginine rich splicing factor 7 [KO:K12896]
10482  NXF1; nuclear RNA export factor 1 [KO:K14284]
56001  NXF2; nuclear RNA export factor 2 [KO:K14284]
728343  NXF2B; nuclear RNA export factor 2B [KO:K14284]
55998  NXF5; nuclear RNA export factor 5 [KO:K14284]
56000  NXF3; nuclear RNA export factor 3 [KO:K14284]
29107  NXT1; nuclear transport factor 2 like export factor 1 [KO:K14285]
55916  NXT2; nuclear transport factor 2 like export factor 2 [KO:K14285]
2733  GLE1; GLE1 RNA export mediator [KO:K18723]
7175  TPR; translocated promoter region, nuclear basket protein [KO:K09291]
10762  NUP50; nucleoporin 50 [KO:K14295]
9972  NUP153; nucleoporin 153 [KO:K14296]
4928  NUP98; nucleoporin 98 and 96 precursor [KO:K14297]
8480  RAE1; ribonucleic acid export 1 [KO:K14298]
6396  SEC13; SEC13 homolog, nuclear pore and COPII coat complex component [KO:K14004]
81929  SEH1L; SEH1 like nucleoporin [KO:K14299]
55746  NUP133; nucleoporin 133 [KO:K14300]
57122  NUP107; nucleoporin 107 [KO:K14301]
79023  NUP37; nucleoporin 37 [KO:K14302]
23279  NUP160; nucleoporin 160 [KO:K14303]
79902  NUP85; nucleoporin 85 [KO:K14304]
348995  NUP43; nucleoporin 43 [KO:K14305]
23636  NUP62; nucleoporin 62 [KO:K14306]
9818  NUP58; nucleoporin 58 [KO:K14307]
53371  NUP54; nucleoporin 54 [KO:K14308]
9688  NUP93; nucleoporin 93 [KO:K14309]
23165  NUP205; nucleoporin 205 [KO:K14310]
23511  NUP188; nucleoporin 188 [KO:K14311]
9631  NUP155; nucleoporin 155 [KO:K14312]
129401  NUP35; nucleoporin 35 [KO:K14313]
23225  NUP210; nucleoporin 210 [KO:K14314]
91181  NUP210L; nucleoporin 210 like [KO:K14314]
55706  NDC1; NDC1 transmembrane nucleoporin [KO:K14315]
100101267  POM121C; POM121 transmembrane nucleoporin C [KO:K14316]
9883  POM121; POM121 transmembrane nucleoporin [KO:K14316]
94026  POM121L2; POM121 transmembrane nucleoporin like 2 [KO:K14316]
8021  NUP214; nucleoporin 214 [KO:K14317]
4927  NUP88; nucleoporin 88 [KO:K14318]
5903  RANBP2; RAN binding protein 2 [KO:K12172] [EC:2.3.2.-]
23064  SETX; senataxin [KO:K10706] [EC:3.6.4.-]
400916  CHCHD10; coiled-coil-helix-coiled-coil-helix domain containing 10 [KO:K22759]
3309  HSPA5; heat shock protein family A (Hsp70) member 5 [KO:K09490] [EC:3.6.4.10]
9217  VAPB; VAMP associated protein B and C [KO:K10707]
22926  ATF6; activating transcription factor 6 [KO:K09054]
1649  DDIT3; DNA damage inducible transcript 3 [KO:K04452]
2081  ERN1; endoplasmic reticulum to nucleus signaling 1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
7494  XBP1; X-box binding protein 1 [KO:K09027]
7186  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
4217  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
100506742  CASP12; caspase 12 (gene/pseudogene) [KO:K04741] [EC:3.4.22.-]
9451  EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
1965  EIF2S1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237]
468  ATF4; activating transcription factor 4 [KO:K04374]
3710  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
10280  SIGMAR1; sigma non-opioid intracellular receptor 1 [KO:K20719]
7124  TNF; tumor necrosis factor [KO:K03156]
7132  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
7133  TNFRSF1B; TNF receptor superfamily member 1B [KO:K05141]
1616  DAXX; death domain associated protein [KO:K02308]
5606  MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
5608  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
5600  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
4842  NOS1; nitric oxide synthase 1 [KO:K13240] [EC:1.14.13.39]
9973  CCS; copper chaperone for superoxide dismutase [KO:K04569]
257202  GPX6; glutathione peroxidase 6 [KO:K00432] [EC:1.11.1.9]
2882  GPX7; glutathione peroxidase 7 [KO:K00432] [EC:1.11.1.9]
2877  GPX2; glutathione peroxidase 2 [KO:K00432] [EC:1.11.1.9]
2878  GPX3; glutathione peroxidase 3 [KO:K00432] [EC:1.11.1.9]
2876  GPX1; glutathione peroxidase 1 [KO:K00432] [EC:1.11.1.9]
2880  GPX5; glutathione peroxidase 5 [KO:K00432] [EC:1.11.1.9]
493869  GPX8; glutathione peroxidase 8 (putative) [KO:K00432] [EC:1.11.1.9]
847  CAT; catalase [KO:K03781] [EC:1.11.1.6]
5630  PRPH; peripherin [KO:K07607]
4747  NEFL; neurofilament light [KO:K04572]
4741  NEFM; neurofilament medium [KO:K04573]
4744  NEFH; neurofilament heavy [KO:K04574]
345456  PFN3; profilin 3 [KO:K05759]
5216  PFN1; profilin 1 [KO:K05759]
5217  PFN2; profilin 2 [KO:K05759]
375189  PFN4; profilin family member 4 [KO:K05759]
71  ACTG1; actin gamma 1 [KO:K05692]
60  ACTB; actin beta [KO:K05692]
310  ANXA7; annexin A7 [KO:K17095]
311  ANXA11; annexin A11 [KO:K17095]
3798  KIF5A; kinesin family member 5A [KO:K10396]
3799  KIF5B; kinesin family member 5B [KO:K10396]
3800  KIF5C; kinesin family member 5C [KO:K10396]
147700  KLC3; kinesin light chain 3 [KO:K10407]
3831  KLC1; kinesin light chain 1 [KO:K10407]
64837  KLC2; kinesin light chain 2 [KO:K10407]
89953  KLC4; kinesin light chain 4 [KO:K10407]
10376  TUBA1B; tubulin alpha 1b [KO:K07374]
7277  TUBA4A; tubulin alpha 4a [KO:K07374]
7278  TUBA3C; tubulin alpha 3c [KO:K07374]
7846  TUBA1A; tubulin alpha 1a [KO:K07374]
84790  TUBA1C; tubulin alpha 1c [KO:K07374]
51807  TUBA8; tubulin alpha 8 [KO:K07374]
112714  TUBA3E; tubulin alpha 3e [KO:K07374]
113457  TUBA3D; tubulin alpha 3d [KO:K07374]
79861  TUBAL3; tubulin alpha like 3 [KO:K07374]
84617  TUBB6; tubulin beta 6 class V [KO:K07375]
203068  TUBB; tubulin beta class I [KO:K07375]
81027  TUBB1; tubulin beta 1 class VI [KO:K07375]
7280  TUBB2A; tubulin beta 2A class IIa [KO:K07375]
10381  TUBB3; tubulin beta 3 class III [KO:K07375]
10382  TUBB4A; tubulin beta 4A class IVa [KO:K07375]
347688  TUBB8; tubulin beta 8 class VIII [KO:K07375]
347733  TUBB2B; tubulin beta 2B class IIb [KO:K07375]
10383  TUBB4B; tubulin beta 4B class IVb [KO:K07375]
1639  DCTN1; dynactin subunit 1 [KO:K04648]
10540  DCTN2; dynactin subunit 2 [KO:K10424]
11258  DCTN3; dynactin subunit 3 [KO:K10425]
51164  DCTN4; dynactin subunit 4 [KO:K10426]
84516  DCTN5; dynactin subunit 5 [KO:K10427]
10671  DCTN6; dynactin subunit 6 [KO:K10428]
10121  ACTR1A; actin related protein 1A [KO:K16575]
10120  ACTR1B; actin related protein 1B [KO:K16575]
55860  ACTR10; actin related protein 10 [KO:K16576]
9001  HAP1; huntingtin associated protein 1 [KO:K04647]
25981  DNAH1; dynein axonemal heavy chain 1 [KO:K10408]
55567  DNAH3; dynein axonemal heavy chain 3 [KO:K10408]
146754  DNAH2; dynein axonemal heavy chain 2 [KO:K10408]
56171  DNAH7; dynein axonemal heavy chain 7 [KO:K10408]
1767  DNAH5; dynein axonemal heavy chain 5 [KO:K10408]
1768  DNAH6; dynein axonemal heavy chain 6 [KO:K10408]
1770  DNAH9; dynein axonemal heavy chain 9 [KO:K10408]
8701  DNAH11; dynein axonemal heavy chain 11 [KO:K10408]
201625  DNAH12; dynein axonemal heavy chain 12 [KO:K10408]
127602  DNAH14; dynein axonemal heavy chain 14 [KO:K10408]
1769  DNAH8; dynein axonemal heavy chain 8 [KO:K10408]
196385  DNAH10; dynein axonemal heavy chain 10 [KO:K10408]
8632  DNAH17; dynein axonemal heavy chain 17 [KO:K10408]
7802  DNALI1; dynein axonemal light intermediate chain 1 [KO:K10410]
27019  DNAI1; dynein axonemal intermediate chain 1 [KO:K10409]
64446  DNAI2; dynein axonemal intermediate chain 2 [KO:K11143]
83544  DNAL1; dynein axonemal light chain 1 [KO:K10411]
10126  DNAL4; dynein axonemal light chain 4 [KO:K10412]
6506  SLC1A2; solute carrier family 1 member 2 [KO:K05613]
4843  NOS2; nitric oxide synthase 2 [KO:K13241] [EC:1.14.13.39]
2890  GRIA1; glutamate ionotropic receptor AMPA type subunit 1 [KO:K05197]
2891  GRIA2; glutamate ionotropic receptor AMPA type subunit 2 [KO:K05198]
2902  GRIN1; glutamate ionotropic receptor NMDA type subunit 1 [KO:K05208]
2903  GRIN2A; glutamate ionotropic receptor NMDA type subunit 2A [KO:K05209]
2904  GRIN2B; glutamate ionotropic receptor NMDA type subunit 2B [KO:K05210]
2905  GRIN2C; glutamate ionotropic receptor NMDA type subunit 2C [KO:K05211]
2906  GRIN2D; glutamate ionotropic receptor NMDA type subunit 2D [KO:K05212]
3084  NRG1; neuregulin 1 [KO:K05455]
9542  NRG2; neuregulin 2 [KO:K05456]
10718  NRG3; neuregulin 3 [KO:K05457]
145957  NRG4; neuregulin 4 [KO:K05458]
2066  ERBB4; erb-b2 receptor tyrosine kinase 4 [KO:K05085] [EC:2.7.10.1]
Compound
C00001  H2O
C00008  ADP
C00025  L-Glutamate
C00027  Hydrogen peroxide
C00039  DNA
C00046  RNA
C00062  L-Arginine
C00070  Copper
C00076  Calcium cation
C00533  Nitric oxide
C00704  Superoxide
C04549  1-Phosphatidyl-1D-myo-inositol 3-phosphate
C16844  Hydroxyl radical
C16845  Peroxynitrite
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Brown RH, Al-Chalabi A
  Title
Amyotrophic Lateral Sclerosis.
  Journal
N Engl J Med 377:162-172 (2017)
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Reference
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Webster CP, Smith EF, Shaw PJ, De Vos KJ
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Protein Homeostasis in Amyotrophic Lateral Sclerosis: Therapeutic Opportunities?
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Front Mol Neurosci 10:123 (2017)
DOI:10.3389/fnmol.2017.00123
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Valko K, Ciesla L
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Amyotrophic lateral sclerosis.
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Mathis S, Goizet C, Soulages A, Vallat JM, Masson GL
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J Neurol Sci 399:217-226 (2019)
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Turner MR, Hardiman O, Benatar M, Brooks BR, Chio A, de Carvalho M, Ince PG, Lin C, Miller RG, Mitsumoto H, Nicholson G, Ravits J, Shaw PJ, Swash M, Talbot K, Traynor BJ, Van den Berg LH, Veldink JH, Vucic S, Kiernan MC
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Lancet Neurol 12:310-22 (2013)
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Inter- and intracellular signaling in amyotrophic lateral sclerosis: role of p38 mitogen-activated protein kinase.
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Neurodegener Dis 2:128-34 (2005)
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Simpson EP, Yen AA, Appel SH
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Oxidative Stress: a common denominator in the pathogenesis of amyotrophic lateral sclerosis.
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Curr Opin Rheumatol 15:730-6 (2003)
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Trends Mol Med 10:393-400 (2004)
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Brain Res 1150:174-81 (2007)
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Stress signaling from the endoplasmic reticulum: A central player in the pathogenesis of amyotrophic lateral sclerosis.
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Sigma-1 receptor and amyotrophic lateral sclerosis.
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Neurology 91:743-747 (2018)
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Axonal transport deficits and neurodegenerative diseases.
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Related
pathway
hsa00190  Oxidative phosphorylation
hsa03013  RNA transport
hsa03050  Proteasome
hsa04010  MAPK signaling pathway
hsa04012  ErbB signaling pathway
hsa04020  Calcium signaling pathway
hsa04115  p53 signaling pathway
hsa04137  Mitophagy - animal
hsa04140  Autophagy - animal
hsa04141  Protein processing in endoplasmic reticulum
hsa04210  Apoptosis
hsa04724  Glutamatergic synapse
hsa04810  Regulation of actin cytoskeleton
KO pathway
ko05014   

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Network (22)   
   KEGG NETWORK (22)   
Disease (2)   
   KEGG DISEASE (2)   
Genome (1)   
   KEGG GENOME (1)   
Gene (364)   
   KEGG GENES (364)   
All databases (389)   

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