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
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
            nt06463  Parkinson 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
            N01402  Manganese to electron transfer in Complex II
            N01403  Zn to anterograde axonal transport
            N01414  Iron to anterograde axonal transport
            N01416  Mercury to NEP-mediated Abeta 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)
            D11210  Flortaucipir F 18 (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)
            D12228  Bepranemab (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 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]
            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]
            29986  SLC39A2; solute carrier family 39 member 2 [KO:K14709]
            29985  SLC39A3; solute carrier family 39 member 3 [KO:K14709]
            27173  SLC39A1; solute carrier family 39 member 1 [KO:K14709]
            55630  SLC39A4; solute carrier family 39 member 4 [KO:K14710]
            283375  SLC39A5; solute carrier family 39 member 5 [KO:K14711]
            25800  SLC39A6; solute carrier family 39 member 6 [KO:K14712]
            7922  SLC39A7; solute carrier family 39 member 7 [KO:K14713]
            64116  SLC39A8; solute carrier family 39 member 8 [KO:K14714]
            55334  SLC39A9; solute carrier family 39 member 9 [KO:K14715]
            57181  SLC39A10; solute carrier family 39 member 10 [KO:K14716]
            201266  SLC39A11; solute carrier family 39 member 11 [KO:K14717]
            221074  SLC39A12; solute carrier family 39 member 12 [KO:K14718]
            91252  SLC39A13; solute carrier family 39 member 13 [KO:K14719]
            23516  SLC39A14; solute carrier family 39 member 14 [KO:K14720]
            4891  SLC11A2; solute carrier family 11 member 2 [KO:K21398]
            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]
            1147  CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:2.7.11.10]
            3551  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
            8517  IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210]
            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
            C00038  Zinc cation
            C00070  Copper
            C00076  Calcium cation
            C00533  Nitric oxide
            C00704  Superoxide
            C01245  D-myo-Inositol 1,4,5-trisphosphate
            C01319  Hg
            C04549  1-Phosphatidyl-1D-myo-inositol 3-phosphate
            C05981  Phosphatidylinositol-3,4,5-trisphosphate
            C14818  Fe2+
            C16514  Amyloid beta protein 40
            C16515  Amyloid beta protein 42
            C16845  Peroxynitrite
            C19610  Manganese(2+)
            C21011  [Protein]-N(epsilon)-(carboxymethyl)lysine
            C21012  [Protein]-N(epsilon)-(carboxyethyl)lysine
            C21013  [Protein]-pyrraline
            C21014  [Protein]-pentosidine
REFERENCE   PMID:15232608
  AUTHORS   Dickson DW
  TITLE     Apoptotic mechanisms in Alzheimer neurofibrillary degeneration: cause or effect?
  JOURNAL   J Clin Invest 114:23-7 (2004)
            DOI:10.1172/JCI22317
REFERENCE   PMID:15750290
  AUTHORS   Takuma K, Yan SS, Stern DM, Yamada K
  TITLE     Mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis in Alzheimer's disease.
  JOURNAL   J Pharmacol Sci 97:312-6 (2005)
            DOI:10.1254/jphs.CPJ04006X
REFERENCE   PMID:18675468
  AUTHORS   Bezprozvanny I, Mattson MP
  TITLE     Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease.
  JOURNAL   Trends Neurosci 31:454-63 (2008)
            DOI:10.1016/j.tins.2008.06.005
REFERENCE   PMID:9848086
  AUTHORS   Holscher C
  TITLE     Possible causes of Alzheimer's disease: amyloid fragments, free radicals, and calcium homeostasis.
  JOURNAL   Neurobiol Dis 5:129-41 (1998)
            DOI:10.1006/nbdi.1998.0193
REFERENCE   PMID:18035450
  AUTHORS   Bojarski L, Herms J, Kuznicki J
  TITLE     Calcium dysregulation in Alzheimer's disease.
  JOURNAL   Neurochem Int 52:621-33 (2008)
            DOI:10.1016/j.neuint.2007.10.002
REFERENCE   PMID:25450339
  AUTHORS   Kondratskyi A, Kondratska K, Skryma R, Prevarskaya N
  TITLE     Ion channels in the regulation of apoptosis.
  JOURNAL   Biochim Biophys Acta 1848:2532-46 (2015)
            DOI:10.1016/j.bbamem.2014.10.030
REFERENCE   PMID:29890840
  AUTHORS   Popugaeva E, Pchitskaya E, Bezprozvanny I
  TITLE     Dysregulation of Intracellular Calcium Signaling in Alzheimer's Disease.
  JOURNAL   Antioxid Redox Signal 29:1176-1188 (2018)
            DOI:10.1089/ars.2018.7506
REFERENCE   PMID:25767489
  AUTHORS   Tan Y, Deng Y, Qing H
  TITLE     Calcium channel blockers and Alzheimer's disease.
  JOURNAL   Neural Regen Res 7:137-40 (2012)
            DOI:10.3969/j.issn.1673-5374.2012.02.010
REFERENCE   PMID:11484003
  AUTHORS   Small DH, Mok SS, Bornstein JC
  TITLE     Alzheimer's disease and Abeta toxicity: from top to bottom.
  JOURNAL   Nat Rev Neurosci 2:595-8 (2001)
            DOI:10.1038/35086072
REFERENCE   PMID:15177383
  AUTHORS   Parihar MS, Hemnani T
  TITLE     Alzheimer's disease pathogenesis and therapeutic interventions.
  JOURNAL   J Clin Neurosci 11:456-67 (2004)
            DOI:10.1016/j.jocn.2003.12.007
REFERENCE   PMID:17568632
  AUTHORS   Cowburn RF, Popescu BO, Ankarcrona M, Dehvari N, Cedazo-Minguez A
  TITLE     Presenilin-mediated signal transduction.
  JOURNAL   Physiol Behav 92:93-7 (2007)
            DOI:10.1016/j.physbeh.2007.05.053
REFERENCE   PMID:22842534
  AUTHORS   Honarnejad K, Herms J
  TITLE     Presenilins: role in calcium homeostasis.
  JOURNAL   Int J Biochem Cell Biol 44:1983-6 (2012)
            DOI:10.1016/j.biocel.2012.07.019
REFERENCE   PMID:21663966
  AUTHORS   Supnet C, Bezprozvanny I
  TITLE     Presenilins function in ER calcium leak and Alzheimer's disease pathogenesis.
  JOURNAL   Cell Calcium 50:303-9 (2011)
            DOI:10.1016/j.ceca.2011.05.013
REFERENCE   PMID:16677790
  AUTHORS   Hauptmann S, Keil U, Scherping I, Bonert A, Eckert A, Muller WE
  TITLE     Mitochondrial dysfunction in sporadic and genetic Alzheimer's disease.
  JOURNAL   Exp Gerontol 41:668-73 (2006)
            DOI:10.1016/j.exger.2006.03.012
REFERENCE   PMID:14557245
  AUTHORS   Chen Y, Liu W, McPhie DL, Hassinger L, Neve RL
  TITLE     APP-BP1 mediates APP-induced apoptosis and DNA synthesis and is increased in Alzheimer's disease brain.
  JOURNAL   J Cell Biol 163:27-33 (2003)
            DOI:10.1083/jcb.200304003
REFERENCE   PMID:24051203
  AUTHORS   Eckert A, Nisbet R, Grimm A, Gotz J
  TITLE     March separate, strike together--role of phosphorylated TAU in mitochondrial dysfunction in Alzheimer's disease.
  JOURNAL   Biochim Biophys Acta 1842:1258-66 (2014)
            DOI:10.1016/j.bbadis.2013.08.013
REFERENCE   PMID:30741722
  AUTHORS   Strickland MR, Holtzman DM
  TITLE     Dr. Jekyll and Mr. Hyde: ApoE explains opposing effects of neuronal LRP1.
  JOURNAL   J Clin Invest 129:969-971 (2019)
            DOI:10.1172/JCI127578
REFERENCE   PMID:10527810
  AUTHORS   Ivins KJ, Thornton PL, Rohn TT, Cotman CW
  TITLE     Neuronal apoptosis induced by beta-amyloid is mediated by caspase-8.
  JOURNAL   Neurobiol Dis 6:440-9 (1999)
            DOI:10.1006/nbdi.1999.0268
REFERENCE   PMID:31655116
  AUTHORS   Sushma, Mondal AC
  TITLE     Role of GPCR signaling and calcium dysregulation in Alzheimer's disease.
  JOURNAL   Mol Cell Neurosci 101:103414 (2019)
            DOI:10.1016/j.mcn.2019.103414
REFERENCE   PMID:18648507
  AUTHORS   Sanz-Blasco S, Valero RA, Rodriguez-Crespo I, Villalobos C, Nunez L
  TITLE     Mitochondrial Ca2+ overload underlies Abeta oligomers neurotoxicity providing an unexpected mechanism of neuroprotection by NSAIDs.
  JOURNAL   PLoS One 3:e2718 (2008)
            DOI:10.1371/journal.pone.0002718
REFERENCE   PMID:20332425
  AUTHORS   Mattson MP
  TITLE     ER calcium and Alzheimer's disease: in a state of flux.
  JOURNAL   Sci Signal 3:pe10 (2010)
            DOI:10.1126/scisignal.3114pe10
REFERENCE   PMID:16394273
  AUTHORS   Lee SY, Hwang DY, Kim YK, Lee JW, Shin IC, Oh KW, Lee MK, Lim JS, Yoon DY, Hwang SJ, Hong JT
  TITLE     PS2 mutation increases neuronal cell vulnerability to neurotoxicants through activation of caspase-3 by enhancing of ryanodine receptor-mediated calcium release.
  JOURNAL   FASEB J 20:151-3 (2006)
            DOI:10.1096/fj.05-4017fje;1
REFERENCE   PMID:11551913
  AUTHORS   Katayama T, Imaizumi K, Honda A, Yoneda T, Kudo T, Takeda M, Mori K, Rozmahel R, Fraser P, George-Hyslop PS, Tohyama M
  TITLE     Disturbed activation of endoplasmic reticulum stress transducers by familial Alzheimer's disease-linked presenilin-1 mutations.
  JOURNAL   J Biol Chem 276:43446-54 (2001)
            DOI:10.1074/jbc.M104096200
REFERENCE   PMID:28057414
  AUTHORS   Lane-Donovan C, Herz J
  TITLE     ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease.
  JOURNAL   Trends Endocrinol Metab 28:273-284 (2017)
            DOI:10.1016/j.tem.2016.12.001
REFERENCE   PMID:27994051
  AUTHORS   Wasser CR, Herz J
  TITLE     Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses.
  JOURNAL   J Biol Chem 292:1330-1338 (2017)
            DOI:10.1074/jbc.R116.766782
REFERENCE   PMID:21116052
  AUTHORS   Lilja AM, Porras O, Storelli E, Nordberg A, Marutle A
  TITLE     Functional interactions of fibrillar and oligomeric amyloid-beta with alpha7 nicotinic receptors in Alzheimer's disease.
  JOURNAL   J Alzheimers Dis 23:335-47 (2011)
            DOI:10.3233/JAD-2010-101242
REFERENCE   PMID:24847263
  AUTHORS   Anastasio TJ
  TITLE     Computational identification of potential multitarget treatments for ameliorating the adverse effects of amyloid-beta on synaptic plasticity.
  JOURNAL   Front Pharmacol 5:85 (2014)
            DOI:10.3389/fphar.2014.00085
REFERENCE   PMID:29378302
  AUTHORS   Vargas LM, Cerpa W, Munoz FJ, Zanlungo S, Alvarez AR
  TITLE     Amyloid-beta oligomers synaptotoxicity: The emerging role of EphA4/c-Abl signaling in Alzheimer's disease.
  JOURNAL   Biochim Biophys Acta Mol Basis Dis 1864:1148-1159 (2018)
            DOI:10.1016/j.bbadis.2018.01.023
REFERENCE   PMID:25394486
  AUTHORS   Tu S, Okamoto S, Lipton SA, Xu H
  TITLE     Oligomeric Abeta-induced synaptic dysfunction in Alzheimer's disease.
  JOURNAL   Mol Neurodegener 9:48 (2014)
            DOI:10.1186/1750-1326-9-48
REFERENCE   PMID:31191253
  AUTHORS   Palomer E, Buechler J, Salinas PC
  TITLE     Wnt Signaling Deregulation in the Aging and Alzheimer's Brain.
  JOURNAL   Front Cell Neurosci 13:227 (2019)
            DOI:10.3389/fncel.2019.00227
REFERENCE   PMID:27807401
  AUTHORS   Vallee A, Lecarpentier Y
  TITLE     Alzheimer Disease: Crosstalk between the Canonical Wnt/Beta-Catenin Pathway and PPARs Alpha and Gamma.
  JOURNAL   Front Neurosci 10:459 (2016)
            DOI:10.3389/fnins.2016.00459
REFERENCE   PMID:19903023
  AUTHORS   Origlia N, Arancio O, Domenici L, Yan SS
  TITLE     MAPK, beta-amyloid and synaptic dysfunction: the role of RAGE.
  JOURNAL   Expert Rev Neurother 9:1635-45 (2009)
            DOI:10.1586/ern.09.107
REFERENCE   PMID:19464758
  AUTHORS   Srikanth V, Maczurek A, Phan T, Steele M, Westcott B, Juskiw D, Munch G
  TITLE     Advanced glycation endproducts and their receptor RAGE in Alzheimer's disease.
  JOURNAL   Neurobiol Aging 32:763-77 (2011)
            DOI:10.1016/j.neurobiolaging.2009.04.016
REFERENCE   PMID:12805290
  AUTHORS   Pigino G, Morfini G, Pelsman A, Mattson MP, Brady ST, Busciglio J
  TITLE     Alzheimer's presenilin 1 mutations impair kinesin-based axonal transport.
  JOURNAL   J Neurosci 23:4499-508 (2003)
            DOI:10.1523/JNEUROSCI.23-11-04499.2003
REFERENCE   PMID:15645263
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  TITLE     Axonal transport defects: a common theme in neurodegenerative diseases.
  JOURNAL   Acta Neuropathol 109:5-13 (2005)
            DOI:10.1007/s00401-004-0952-x
REFERENCE   PMID:26074767
  AUTHORS   Ferreira ST, Lourenco MV, Oliveira MM, De Felice FG
  TITLE     Soluble amyloid-beta oligomers as synaptotoxins leading to cognitive impairment in Alzheimer's disease.
  JOURNAL   Front Cell Neurosci 9:191 (2015)
            DOI:10.3389/fncel.2015.00191
REFERENCE   PMID:24529521
  AUTHORS   De Felice FG, Lourenco MV, Ferreira ST
  TITLE     How does brain insulin resistance develop in Alzheimer's disease?
  JOURNAL   Alzheimers Dement 10:S26-32 (2014)
            DOI:10.1016/j.jalz.2013.12.004
REFERENCE   PMID:26136647
  AUTHORS   Bedse G, Di Domenico F, Serviddio G, Cassano T
  TITLE     Aberrant insulin signaling in Alzheimer's disease: current knowledge.
  JOURNAL   Front Neurosci 9:204 (2015)
            DOI:10.3389/fnins.2015.00204
REFERENCE   PMID:20101724
  AUTHORS   Funderburk SF, Marcellino BK, Yue Z
  TITLE     Cell "self-eating" (autophagy) mechanism in Alzheimer's disease.
  JOURNAL   Mt Sinai J Med 77:59-68 (2010)
            DOI:10.1002/msj.20161
REL_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
///
