KEGG   PATHWAY: hsa05010
Entry
hsa05010                    Pathway                                

Name
Alzheimer disease - Homo sapiens (human)
Description
Alzheimer disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-beta (Abeta), a major component of senile plaques, has various pathological effects on cell and organelle function. To date genetic studies have revealed four genes that may be linked to autosomal dominant or familial early onset AD (FAD). These four genes include: amyloid precursor protein (APP), presenilin 1 (PS1), presenilin 2 (PS2) and apolipoprotein E (ApoE). All mutations associated with APP and PS proteins can lead to an increase in the production of Abeta peptides, specfically the more amyloidogenic form, Abeta42. It was proposed that Abeta form Ca2+ permeable pores and bind to and modulate multiple synaptic proteins, including NMDAR, mGluR5 and VGCC, leading to the overfilling of neurons with calcium ions. Consequently, cellular Ca2+ disruptions will lead to neuronal apoptosis, autophagy deficits, mitochondrial abnormality, defective neurotransmission, impaired synaptic plasticity and neurodegeneration in AD. FAD-linked PS1 mutation downregulates the unfolded protein response and leads to vulnerability to ER stress.
Class
Human Diseases; Neurodegenerative disease
Pathway map
hsa05010  Alzheimer disease
hsa05010

Network
nt06410  Calcium signaling
nt06412  Unfolded protein response (UPR) signaling
nt06414  Apoptosis
nt06417  AGE-RAGE signaling
nt06418  Oxidative phosphorylation
nt06419  Microtubule-based transport
nt06420  Ubiquitin-proteasome system
nt06460  Alzheimer disease
  Element
N00996  Mutation-caused aberrant Abeta to AGE-RAGE signaling pathway
N00997  Mutation-caused aberrant Abeta to electron transfer in Complex I
N00999  Mutation-caused aberrant Abeta to electron transfer in Complex IV
N01001  Mutation-caused aberrant Abeta to mAchR-Ca2+ -apoptotic pathway
N01002  Mutation-caused aberrant Abeta to mGluR5-Ca2+ -apoptotic pathway
N01003  Mutation-caused aberrant Abeta to transport of calcium
N01004  Mutation-caused aberrant Abeta to VGCC-Ca2+ -apoptotic pathway
N01005  Mutation-caused aberrant Abeta to crosstalk between extrinsic and intrinsic apoptotic pathways
N01006  Mutation-caused aberrant Abeta to VGCC-Ca2+ -apoptotic pathway
N01007  Mutation-caused aberrant PSEN to mGluR5-Ca2+ -apoptotic pathway
N01008  Mutation-caused aberrant PSEN1 to mGluR5-Ca2+ -apoptotic pathway
N01010  Mutation-caused aberrant PSEN1 to PERK-ATF4 signaling pathway
N01012  Mutation-caused aberrant PSEN1 to IRE1a-XBP1 signaling pathway
N01014  Mutation-caused aberrant Abeta to IRE1a-JNK signaling pathway
N01016  Mutation-caused aberrant PSEN1 to ATF6-mediated transcription
N01017  Mutation-caused aberrant PSEN1 to anterograde axonal transport
N01018  Mutation-caused aberrant Abeta to anterograde axonal transport
N01060  Mutation-caused aberrant Abeta to 26S proteasome-mediated protein degradation
Disease
H00056  Alzheimer disease
Drug
D04905  Memantine hydrochloride (JAN/USP)
D08174  Memantine (INN)
D08869  Begacestat (USAN/INN)
D09010  Tarenflurbil (USAN/INN)
D09377  Semagacestat (USAN/INN)
D09869  Avagacestat (USAN)
D10739  Verubecestat (JAN/USAN/INN)
D10946  Lanabecestat (USAN)
D10947  Lanabecestat camsylate (USAN)
D11293  Gosuranemab (USAN)
D11384  Hydromethylthionine mesylate (USAN)
D11427  Hydromethylthionine (USAN)
D11456  Atabecestat (USAN/INN)
D11509  Elenbecestat (JAN/USAN)
D11533  Zagotenemab (USAN)
D11687  Semorinemab (USAN/INN)
D11690  Umibecestat (USAN/INN)
D11840  Tilavonemab (USAN/INN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
102  ADAM10; ADAM metallopeptidase domain 10 [KO:K06704] [EC:3.4.24.81]
6868  ADAM17; ADAM metallopeptidase domain 17 [KO:K06059] [EC:3.4.24.86]
351  APP; amyloid beta precursor protein [KO:K04520]
8883  NAE1; NEDD8 activating enzyme E1 subunit 1 [KO:K04532]
322  APBB1; amyloid beta precursor protein binding family B member 1 [KO:K04529]
2597  GAPDH; glyceraldehyde-3-phosphate dehydrogenase [KO:K00134] [EC:1.2.1.12]
23621  BACE1; beta-secretase 1 [KO:K04521] [EC:3.4.23.46]
25825  BACE2; beta-secretase 2 [KO:K07747] [EC:3.4.23.45]
10313  RTN3; reticulon 3 [KO:K20723]
57142  RTN4; reticulon 4 [KO:K20720]
55851  PSENEN; presenilin enhancer, gamma-secretase subunit [KO:K06170]
5663  PSEN1; presenilin 1 [KO:K04505] [EC:3.4.23.-]
5664  PSEN2; presenilin 2 [KO:K04522] [EC:3.4.23.-]
23385  NCSTN; nicastrin [KO:K06171]
51107  APH1A; aph-1 homolog A, gamma-secretase subunit [KO:K06172]
83464  APH1B; aph-1 homolog B, gamma-secretase subunit [KO:K06172]
3416  IDE; insulin degrading enzyme [KO:K01408] [EC:3.4.24.56]
4311  MME; membrane metalloendopeptidase [KO:K01389] [EC:3.4.24.11]
4137  MAPT; microtubule associated protein tau [KO:K04380]
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]
3028  HSD17B10; hydroxysteroid 17-beta dehydrogenase 10 [KO:K08683] [EC:1.1.1.35 1.1.1.178]
5481  PPID; peptidylprolyl isomerase D [KO:K05864] [EC:5.2.1.8]
7416  VDAC1; voltage dependent anion channel 1 [KO:K05862]
7417  VDAC2; voltage dependent anion channel 2 [KO:K15040]
7419  VDAC3; voltage dependent anion channel 3 [KO:K15041]
291  SLC25A4; solute carrier family 25 member 4 [KO:K05863]
292  SLC25A5; solute carrier family 25 member 5 [KO:K05863]
293  SLC25A6; solute carrier family 25 member 6 [KO:K05863]
83447  SLC25A31; solute carrier family 25 member 31 [KO:K05863]
10105  PPIF; peptidylprolyl isomerase F [KO:K09565] [EC:5.2.1.8]
4023  LPL; lipoprotein lipase [KO:K01059] [EC:3.1.1.34]
348  APOE; apolipoprotein E [KO:K04524]
4035  LRP1; LDL receptor related protein 1 [KO:K04550]
355  FAS; Fas cell surface death receptor [KO:K04390]
7132  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
8772  FADD; Fas associated via death domain [KO:K02373]
841  CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
637  BID; BH3 interacting domain death agonist [KO:K04726]
810  CALML3; calmodulin like 3 [KO:K02183]
805  CALM2; calmodulin 2 [KO:K02183]
808  CALM3; calmodulin 3 [KO:K02183]
801  CALM1; calmodulin 1 [KO:K02183]
163688  CALML6; calmodulin like 6 [KO:K02183]
51806  CALML5; calmodulin like 5 [KO:K02183]
91860  CALML4; calmodulin like 4 [KO:K02183]
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]
572  BAD; BCL2 associated agonist of cell death [KO:K02158]
54205  CYCS; cytochrome c, somatic [KO:K08738]
317  APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
842  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
836  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
1128  CHRM1; cholinergic receptor muscarinic 1 [KO:K04129]
1131  CHRM3; cholinergic receptor muscarinic 3 [KO:K04131]
1133  CHRM5; cholinergic receptor muscarinic 5 [KO:K04133]
2915  GRM5; glutamate metabotropic receptor 5 [KO:K04604]
2776  GNAQ; G protein subunit alpha q [KO:K04634]
23236  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
5330  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
5331  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
5332  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
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]
775  CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
776  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
778  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
779  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
1139  CHRNA7; cholinergic receptor nicotinic alpha 7 subunit [KO:K04809]
90550  MCU; mitochondrial calcium uniporter [KO:K20858]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
6263  RYR3; ryanodine receptor 3 [KO:K04963]
3708  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
3709  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
3710  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
487  ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853] [EC:7.2.2.10]
489  ATP2A3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 [KO:K05853] [EC:7.2.2.10]
488  ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853] [EC:7.2.2.10]
22926  ATF6; activating transcription factor 6 [KO:K09054]
7494  XBP1; X-box binding protein 1 [KO:K09027]
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.-]
9451  EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
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]
5609  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
1965  EIF2S1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237]
468  ATF4; activating transcription factor 4 [KO:K04374]
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, 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, 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; adhesion regulating molecule 1 [KO:K06691]
7979  SEM1; SEM1 26S proteasome complex subunit [KO:K10881]
100506742  CASP12; caspase 12 (gene/pseudogene) [KO:K04741] [EC:3.4.22.-]
4842  NOS1; nitric oxide synthase 1 [KO:K13240] [EC:1.14.13.39]
823  CAPN1; calpain 1 [KO:K01367] [EC:3.4.22.52]
824  CAPN2; calpain 2 [KO:K03853] [EC:3.4.22.53]
8851  CDK5R1; cyclin dependent kinase 5 regulatory subunit 1 [KO:K11716]
1020  CDK5; cyclin dependent kinase 5 [KO:K02090] [EC:2.7.11.22]
2932  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
840  CASP7; caspase 7 [KO:K04397] [EC:3.4.22.60]
22943  DKK1; dickkopf WNT signaling pathway inhibitor 1 [KO:K02165]
27123  DKK2; dickkopf WNT signaling pathway inhibitor 2 [KO:K02165]
27121  DKK4; dickkopf WNT signaling pathway inhibitor 4 [KO:K02165]
7471  WNT1; Wnt family member 1 [KO:K03209]
7472  WNT2; Wnt family member 2 [KO:K00182]
7482  WNT2B; Wnt family member 2B [KO:K00182]
7473  WNT3; Wnt family member 3 [KO:K00312]
89780  WNT3A; Wnt family member 3A [KO:K00312]
54361  WNT4; Wnt family member 4 [KO:K00408]
7474  WNT5A; Wnt family member 5A [KO:K00444]
81029  WNT5B; Wnt family member 5B [KO:K00444]
7475  WNT6; Wnt family member 6 [KO:K00445]
7476  WNT7A; Wnt family member 7A [KO:K00572]
7477  WNT7B; Wnt family member 7B [KO:K00572]
7478  WNT8A; Wnt family member 8A [KO:K00714]
7479  WNT8B; Wnt family member 8B [KO:K00714]
7483  WNT9A; Wnt family member 9A [KO:K01064]
7484  WNT9B; Wnt family member 9B [KO:K01064]
7480  WNT10B; Wnt family member 10B [KO:K01357]
80326  WNT10A; Wnt family member 10A [KO:K01357]
7481  WNT11; Wnt family member 11 [KO:K01384]
51384  WNT16; Wnt family member 16 [KO:K01558]
8321  FZD1; frizzled class receptor 1 [KO:K02432]
8324  FZD7; frizzled class receptor 7 [KO:K02432]
2535  FZD2; frizzled class receptor 2 [KO:K02235]
7976  FZD3; frizzled class receptor 3 [KO:K02329]
8322  FZD4; frizzled class receptor 4 [KO:K02354]
7855  FZD5; frizzled class receptor 5 [KO:K02375]
8325  FZD8; frizzled class receptor 8 [KO:K02375]
8323  FZD6; frizzled class receptor 6 [KO:K02376]
11211  FZD10; frizzled class receptor 10 [KO:K02842]
8326  FZD9; frizzled class receptor 9 [KO:K02842]
4041  LRP5; LDL receptor related protein 5 [KO:K03068]
4040  LRP6; LDL receptor related protein 6 [KO:K03068]
1454  CSNK1E; casein kinase 1 epsilon [KO:K08960] [EC:2.7.11.1]
102800317  TPTEP2-CSNK1E; TPTEP2-CSNK1E readthrough [KO:K08960] [EC:2.7.11.1]
1857  DVL3; dishevelled segment polarity protein 3 [KO:K02353]
1856  DVL2; dishevelled segment polarity protein 2 [KO:K02353]
1855  DVL1; dishevelled segment polarity protein 1 [KO:K02353]
10023  FRAT1; FRAT regulator of WNT signaling pathway 1 [KO:K03069]
23401  FRAT2; FRAT regulator of WNT signaling pathway 2 [KO:K03096]
1457  CSNK2A1; casein kinase 2 alpha 1 [KO:K03097] [EC:2.7.11.1]
1459  CSNK2A2; casein kinase 2 alpha 2 [KO:K03097] [EC:2.7.11.1]
283106  CSNK2A3; casein kinase 2 alpha 3 [KO:K03097] [EC:2.7.11.1]
1460  CSNK2B; casein kinase 2 beta [KO:K03115]
8312  AXIN1; axin 1 [KO:K02157]
8313  AXIN2; axin 2 [KO:K04385]
324  APC; APC regulator of WNT signaling pathway [KO:K02085]
10297  APC2; APC regulator of WNT signaling pathway 2 [KO:K02085]
1499  CTNNB1; catenin beta 1 [KO:K02105]
122011  CSNK1A1L; casein kinase 1 alpha 1 like [KO:K08957] [EC:2.7.11.1]
1452  CSNK1A1; casein kinase 1 alpha 1 [KO:K08957] [EC:2.7.11.1]
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]
177  AGER; advanced glycosylation end-product specific receptor [KO:K19722]
3265  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
3845  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
4893  NRAS; NRAS proto-oncogene, GTPase [KO:K07828]
369  ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
673  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
5894  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
27035  NOX1; NADPH oxidase 1 [KO:K08008]
1536  CYBB; cytochrome b-245 beta chain [KO:K21421] [EC:1.-.-.-]
50507  NOX4; NADPH oxidase 4 [KO:K21423] [EC:1.6.3.-]
5970  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
4790  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
4843  NOS2; nitric oxide synthase 2 [KO:K13241] [EC:1.14.13.39]
5743  PTGS2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
7124  TNF; tumor necrosis factor [KO:K03156]
3569  IL6; interleukin 6 [KO:K05405]
3552  IL1A; interleukin 1 alpha [KO:K04383]
3553  IL1B; interleukin 1 beta [KO:K04519]
1435  CSF1; colony stimulating factor 1 [KO:K05453]
6622  SNCA; synuclein alpha [KO:K04528]
5610  EIF2AK2; eukaryotic translation initiation factor 2 alpha kinase 2 [KO:K16195] [EC:2.7.11.1]
3551  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
1147  CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:2.7.11.10]
10888  GPR83; G protein-coupled receptor 83 [KO:K04210]
3630  INS; insulin [KO:K04526]
3643  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
3667  IRS1; insulin receptor substrate 1 [KO:K16172]
8660  IRS2; insulin receptor substrate 2 [KO:K07187]
8471  IRS4; insulin receptor substrate 4 [KO:K17446]
5295  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
5296  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
5290  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
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]
Compound
C00027  Hydrogen peroxide
C00070  Copper
C00076  Calcium cation
C00533  Nitric oxide
C00704  Superoxide
C01245  D-myo-Inositol 1,4,5-trisphosphate
C04549  1-Phosphatidyl-1D-myo-inositol 3-phosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C14818  Fe2+
C16514  Beta-amyloid protein 40
C16515  Beta-amyloid protein 42
C16845  Peroxynitrite
C21011  [Protein]-N(epsilon)-(carboxymethyl)lysine
C21012  [Protein]-N(epsilon)-(carboxyethyl)lysine
C21013  [Protein]-pyrraline
C21014  [Protein]-pentosidine
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Apoptotic mechanisms in Alzheimer neurofibrillary degeneration: cause or effect?
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J Clin Invest 114:23-7 (2004)
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Mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis in Alzheimer's disease.
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J Pharmacol Sci 97:312-6 (2005)
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Trends Neurosci 31:454-63 (2008)
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Calcium dysregulation in Alzheimer's disease.
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J Clin Neurosci 11:456-67 (2004)
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Presenilin-mediated signal transduction.
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Physiol Behav 92:93-7 (2007)
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Exp Gerontol 41:668-73 (2006)
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APP-BP1 mediates APP-induced apoptosis and DNA synthesis and is increased in Alzheimer's disease brain.
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J Cell Biol 163:27-33 (2003)
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March separate, strike together--role of phosphorylated TAU in mitochondrial dysfunction in Alzheimer's disease.
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Biochim Biophys Acta 1842:1258-66 (2014)
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Strickland MR, Holtzman DM
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Mol Cell Neurosci 101:103414 (2019)
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Mitochondrial Ca2+ overload underlies Abeta oligomers neurotoxicity providing an unexpected mechanism of neuroprotection by NSAIDs.
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PLoS One 3:e2718 (2008)
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ER calcium and Alzheimer's disease: in a state of flux.
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PS2 mutation increases neuronal cell vulnerability to neurotoxicants through activation of caspase-3 by enhancing of ryanodine receptor-mediated calcium release.
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Front Cell Neurosci 9:191 (2015)
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How does brain insulin resistance develop in Alzheimer's disease?
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Alzheimers Dement 10:S26-32 (2014)
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Reference
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Aberrant insulin signaling in Alzheimer's disease: current knowledge.
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Front Neurosci 9:204 (2015)
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Reference
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DOI:10.1002/msj.20161
Related
pathway
hsa00190  Oxidative phosphorylation
hsa03050  Proteasome
hsa04020  Calcium signaling pathway
hsa04140  Autophagy - animal
hsa04141  Protein processing in endoplasmic reticulum
hsa04210  Apoptosis
hsa04310  Wnt signaling pathway
hsa04910  Insulin signaling pathway
hsa04933  AGE-RAGE signaling pathway in diabetic complications
KO pathway
ko05010   
LinkDB

DBGET integrated database retrieval system