KEGG   PATHWAY: rno05010
Entry
rno05010                    Pathway                                
Name
Alzheimer disease - Rattus norvegicus (rat)
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
rno05010  Alzheimer disease
rno05010

Organism
Rattus norvegicus (rat) [GN:rno]
Gene
29650  Adam10; disintegrin and metalloproteinase domain-containing protein 10 precursor [KO:K06704] [EC:3.4.24.81]
57027  Adam17; disintegrin and metalloproteinase domain-containing protein 17 precursor [KO:K06059] [EC:3.4.24.86]
54226  App; amyloid-beta A4 protein precursor [KO:K04520]
84019  Nae1; NEDD8-activating enzyme E1 regulatory subunit [KO:K04532]
29722  Apbb1; amyloid-beta A4 precursor protein-binding family B member 1 [KO:K04529]
24383  Gapdh; glyceraldehyde-3-phosphate dehydrogenase [KO:K00134] [EC:1.2.1.12]
303448  uncharacterized protein LOC303448 [KO:K00134] [EC:1.2.1.12]
290604  RGD1564958; glyceraldehyde-3-phosphate dehydrogenase-like [KO:K00134] [EC:1.2.1.12]
29392  Bace1; beta-secretase 1 precursor [KO:K04521] [EC:3.4.23.46]
288227  Bace2; beta-secretase 2 precursor [KO:K07747] [EC:3.4.23.45]
140945  Rtn3; reticulon-3 isoform A [KO:K20723]
83765  Rtn4; reticulon-4 [KO:K20720]
292788  Psenen; gamma-secretase subunit PEN-2 [KO:K06170]
29192  Psen1; presenilin-1 [KO:K04505] [EC:3.4.23.-]
81751  Psen2; presenilin-2 [KO:K04522] [EC:3.4.23.-]
289231  Ncstn; nicastrin precursor [KO:K06171]
365872  Aph1a; gamma-secretase subunit APH-1A [KO:K06172]
300802  Aph1b; gamma-secretase subunit APH-1B [KO:K06172]
691658  gamma-secretase subunit APH-1B isoform X4 [KO:K06172]
25700  Ide; insulin-degrading enzyme [KO:K01408] [EC:3.4.24.56]
24590  Mme; neprilysin [KO:K01389] [EC:3.4.24.11]
29477  Mapt; microtubule-associated protein tau [KO:K04380]
26193  ND1; NADH dehydrogenase subunit 1 [KO:K03878] [EC:7.1.1.2]
26194  ND2; NADH dehydrogenase subunit 2 [KO:K03879] [EC:7.1.1.2]
26199  ND3; NADH dehydrogenase subunit 3 [KO:K03880] [EC:7.1.1.2]
26201  ND4; NADH dehydrogenase subunit 4 [KO:K03881] [EC:7.1.1.2]
26200  ND4L; NADH dehydrogenase subunit 4L [KO:K03882] [EC:7.1.1.2]
26202  ND5; NADH dehydrogenase subunit 5 [KO:K03883] [EC:7.1.1.2]
26203  ND6; NADH dehydrogenase subunit 6 [KO:K03884] [EC:7.1.1.2]
293655  Ndufv1; NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial [KO:K03942] [EC:7.1.1.2]
81728  Ndufv2; NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial precursor [KO:K03943] [EC:7.1.1.2]
64539  Ndufv3; NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial isoform 2 [KO:K03944]
363441  Ndufa1; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 [KO:K03945]
291660  Ndufa2; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 [KO:K03946]
691001  Ndufa3; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 [KO:K03947]
684509  NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 [KO:K03947]
681024  Ndufa4; cytochrome c oxidase subunit NDUFA4 [KO:K03948]
100362331  Ndufa4l2; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4-like 2 [KO:K03948]
25488  Ndufa5; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 [KO:K03949]
315167  Ndufa6; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6 [KO:K03950]
299643  Ndufa7; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7 [KO:K03951]
296658  Ndufa8; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 [KO:K03952]
362440  Ndufa9; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial [KO:K03953]
316632  Ndufa10l1; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 10-like [KO:K03954]
678759  Ndufa10; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial precursor [KO:K03954]
293453  Ndufab1; acyl carrier protein, mitochondrial [KO:K03955]
301123  Ndufa11; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 [KO:K03956]
299739  Ndufa12; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 [KO:K11352]
100911483  Ndufa13; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 [KO:K11353]
362344  Ndufb2; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial [KO:K03958]
301427  Ndufb3; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 [KO:K03959]
288088  Ndufb4; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4 [KO:K03960]
294964  Ndufb5; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mitochondrial [KO:K03961]
297990  Ndufb6; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6 [KO:K03962]
361385  Ndufb7; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7 [KO:K03963]
293991  Ndufb8; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial [KO:K03964]
299954  Ndufb9; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 [KO:K03965]
681418  Ndufb10; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 [KO:K03966]
299310  Ndufb11; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial [KO:K11351]
301458  Ndufs1; NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial precursor [KO:K03934] [EC:7.1.1.2]
289218  Ndufs2; NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial precursor [KO:K03935] [EC:7.1.1.2]
295923  Ndufs3; NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial [KO:K03936] [EC:7.1.1.2]
499529  Ndufs4; NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial precursor [KO:K03937]
362588  Ndufs5; NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 [KO:K03938]
100363268  NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 [KO:K03938]
29478  Ndufs6; NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial precursor [KO:K03939]
679739  NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial [KO:K03939]
362837  Ndufs7; NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial [KO:K03940] [EC:7.1.1.2]
293652  Ndufs8; NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial [KO:K03941] [EC:7.1.1.2]
689938  Ndufc1; NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial [KO:K03967]
293130  Ndufc2; NADH dehydrogenase [ubiquinone] 1 subunit C2 [KO:K03968]
157074  Sdha; succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial precursor [KO:K00234] [EC:1.3.5.1]
298596  Sdhb; succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial precursor [KO:K00235] [EC:1.3.5.1]
289217  Sdhc; succinate dehydrogenase cytochrome b560 subunit, mitochondrial [KO:K00236]
363061  Sdhd; succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial [KO:K00237]
291103  Uqcrfs1; cytochrome b-c1 complex subunit Rieske, mitochondrial [KO:K00411] [EC:7.1.1.8]
26192  CYTB; cytochrome b [KO:K00412]
300047  Cyc1; cytochrome c-1 [KO:K00413]
301011  Uqcrc1; cytochrome b-c1 complex subunit 1, mitochondrial precursor [KO:K00414]
293448  Uqcrc2; cytochrome b-c1 complex subunit 2, mitochondrial precursor [KO:K00415]
366448  Uqcrh; cytochrome b-c1 complex subunit 6, mitochondrial [KO:K00416]
362897  Uqcrb; cytochrome b-c1 complex subunit 7 [KO:K00417]
497902  Uqcrq; cytochrome b-c1 complex subunit 8 [KO:K00418]
685322  Uqcr10; ubiquinol-cytochrome c reductase complex 7.2kDa protein [KO:K00419]
100361126  RGD2320734; cytochrome b-c1 complex subunit 9 [KO:K00419]
690848  Uqcr11; ubiquinol-cytochrome c reductase, complex III subunit XI [KO:K00420]
26204  COX3; cytochrome c oxidase subunit III [KO:K02262]
26195  COX1; cytochrome c oxidase subunit I [KO:K02256] [EC:7.1.1.9]
26198  COX2; cytochrome c oxidase subunit II [KO:K02261]
84683  Cox4i2; cytochrome c oxidase subunit 4 isoform 2, mitochondrial isoform 2 precursor [KO:K02263]
29445  Cox4i1; cytochrome c oxidase subunit 4 isoform 1, mitochondrial precursor [KO:K02263]
252934  Cox5a; cytochrome c oxidase subunit 5A, mitochondrial precursor [KO:K02264]
94194  Cox5b; cytochrome c oxidase subunit 5B, mitochondrial precursor [KO:K02265]
25278  Cox6a2; cytochrome c oxidase subunit 6A2, mitochondrial precursor [KO:K02266]
25282  Cox6a1; cytochrome c oxidase subunit 6A1, mitochondrial precursor [KO:K02266]
688869  Cox6b1; cytochrome c oxidase subunit 6B1 [KO:K02267]
654441  Cox6b2; cytochrome c oxidase subunit 6B2 [KO:K02267]
54322  Cox6c; cytochrome c oxidase subunit 6C-2 [KO:K02268]
29507  Cox7a2; cytochrome c oxidase subunit 7A2, mitochondrial precursor [KO:K02270]
298762  Cox7a2l; cytochrome c oxidase subunit 7A2 like [KO:K02270]
688386  Cox7a2l2; cytochrome c oxidase subunit 7A2, mitochondrial [KO:K02270]
687508  cytochrome c oxidase subunit 7A1, mitochondrial isoform X2 [KO:K02270]
303393  Cox7b; cytochrome c oxidase subunit 7B, mitochondrial precursor [KO:K02271]
100361960  Cox7b2; cytochrome c oxidase subunit 7B, mitochondrial [KO:K02271]
100188937  Cox7c; cytochrome c oxidase subunit 7C, mitochondrial [KO:K02272]
25250  Cox8b; cytochrome c oxidase subunit 8B, mitochondrial precursor [KO:K02273]
360229  Cox8c; cytochrome c oxidase subunit 8C, mitochondrial [KO:K02273]
171335  Cox8a; cytochrome c oxidase subunit 8A, mitochondrial precursor [KO:K02273]
65262  Atp5f1a; ATP synthase subunit alpha, mitochondrial precursor [KO:K02132]
171374  Atp5f1b; ATP synthase subunit beta, mitochondrial precursor [KO:K02133] [EC:7.1.2.2]
116550  Atp5f1c; ATP synthase subunit gamma, mitochondrial [KO:K02136]
245965  Atp5f1d; ATP synthase subunit delta, mitochondrial precursor [KO:K02134]
245958  Atp5f1e; ATP synthase subunit epsilon, mitochondrial [KO:K02135]
26197  ATP6; ATP synthase F0 subunit 6 [KO:K02126]
171375  Atp5pb; ATP synthase F(0) complex subunit B1, mitochondrial precursor [KO:K02127]
171082  Atp5mc2; ATP synthase F(0) complex subunit C2, mitochondrial precursor [KO:K02128]
114630  Atp5mc3; ATP synthase F(0) complex subunit C3, mitochondrial precursor [KO:K02128]
29754  Atp5mc1; ATP synthase F(0) complex subunit C1, mitochondrial precursor [KO:K02128]
641434  Atp5pd; ATP synthase subunit d, mitochondrial [KO:K02138]
192241  Atp5po; ATP synthase subunit O, mitochondrial precursor [KO:K02137]
94271  Atp5pf; ATP synthase-coupling factor 6, mitochondrial precursor [KO:K02131]
26196  ATP8; ATP synthase F0 subunit 8 [KO:K02125]
63864  Hsd17b10; 3-hydroxyacyl-CoA dehydrogenase type-2 [KO:K08683] [EC:1.1.1.35 1.1.1.178]
361967  Ppid; peptidyl-prolyl cis-trans isomerase D [KO:K05864] [EC:5.2.1.8]
83529  Vdac1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
83531  Vdac2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
83532  Vdac3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
25176  Slc25a5; ADP/ATP translocase 2 [KO:K05863]
85333  Slc25a4; ADP/ATP translocase 1 [KO:K05863]
689108  Slc25a31; ADP/ATP translocase 4 [KO:K05863]
282819  Ppif; peptidyl-prolyl cis-trans isomerase F, mitochondrial precursor [KO:K09565] [EC:5.2.1.8]
24539  Lpl; lipoprotein lipase precursor [KO:K01059] [EC:3.1.1.34]
25728  Apoe; apolipoprotein E precursor [KO:K04524]
299858  Lrp1; prolow-density lipoprotein receptor-related protein 1 precursor [KO:K04550]
246097  Fas; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390]
25625  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158]
266610  Fadd; FAS-associated death domain protein [KO:K02373]
64044  Casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
64625  Bid; BH3-interacting domain death agonist [KO:K04726]
50663  Calm2; calmodulin-2 [KO:K02183]
24242  Calm1; calmodulin-1 [KO:K02183]
24244  Calm3; calmodulin-3 [KO:K02183]
364774  Calml5; calmodulin-like protein 5 [KO:K02183]
307100  Calml3; calmodulin-like protein 3 [KO:K02183]
691455  Calml4; calmodulin-like protein 4 [KO:K02183]
24674  Ppp3ca; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
24675  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
171378  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
29748  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
29749  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
64639  Bad; bcl2-associated agonist of cell death [KO:K02158]
25309  Cycs; cytochrome c, somatic [KO:K08738]
25310  Cyct; cytochrome c, testis-specific [KO:K08738]
100363502  cytochrome c, somatic [KO:K08738]
78963  Apaf1; apoptotic protease-activating factor 1 [KO:K02084]
58918  Casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
25402  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
25229  Chrm1; muscarinic acetylcholine receptor M1 [KO:K04129]
24260  Chrm3; muscarinic acetylcholine receptor M3 [KO:K04131]
53949  Chrm5; muscarinic acetylcholine receptor M5 [KO:K04133]
24418  Grm5; metabotropic glutamate receptor 5 precursor [KO:K04604]
81666  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
24654  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
29322  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
85240  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
25031  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
24408  Grin1; glutamate receptor ionotropic, NMDA 1 isoform 1a precursor [KO:K05208]
24409  Grin2a; glutamate receptor ionotropic, NMDA 2A precursor [KO:K05209]
24410  Grin2b; glutamate receptor ionotropic, NMDA 2B precursor [KO:K05210]
24411  Grin2c; glutamate receptor ionotropic, NMDA 2C [KO:K05211]
24412  Grin2d; glutamate receptor ionotropic, NMDA 2D precursor [KO:K05212]
24239  Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
29716  Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
114493  Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
682930  Cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
25302  Chrna7; neuronal acetylcholine receptor subunit alpha-7 precursor [KO:K04809]
294560  Mcu; calcium uniporter protein, mitochondrial precursor [KO:K20858]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
170546  Ryr3; LOW QUALITY PROTEIN: ryanodine receptor 3 [KO:K04963]
25262  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform 3 [KO:K04958]
81678  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
25679  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
116601  Atp2a1; sarcoplasmic/endoplasmic reticulum calcium ATPase 1 [KO:K05853] [EC:7.2.2.10]
25391  Atp2a3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3 [KO:K05853] [EC:7.2.2.10]
29693  Atp2a2; sarcoplasmic/endoplasmic reticulum calcium ATPase 2 isoform b [KO:K05853] [EC:7.2.2.10]
304962  Atf6; cyclic AMP-dependent transcription factor ATF-6 alpha [KO:K09054]
289754  Xbp1; X-box-binding protein 1 isoform XBP1(U) [KO:K09027]
29467  Ddit3; DNA damage-inducible transcript 3 protein [KO:K04452]
498013  Ern1; serine/threonine-protein kinase/endoribonuclease IRE1 [KO:K08852] [EC:2.7.11.1 3.1.26.-]
29702  Eif2ak3; eukaryotic translation initiation factor 2-alpha kinase 3 precursor [KO:K08860] [EC:2.7.11.1]
311786  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
365057  Map3k5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
363855  Map2k7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
25272  Mapk10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
50658  Mapk9; mitogen-activated protein kinase 9 isoform 2 [KO:K04440] [EC:2.7.11.24]
116554  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
54318  Eif2s1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
79255  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
29673  Psma6; proteasome subunit alpha type-6 [KO:K02730] [EC:3.4.25.1]
29669  Psma2; proteasome subunit alpha type-2 [KO:K02726] [EC:3.4.25.1]
29671  Psma4; proteasome subunit alpha type-4 [KO:K02728] [EC:3.4.25.1]
29674  Psma7; proteasome subunit alpha type-7 [KO:K02731] [EC:3.4.25.1]
364814  Psma8; proteasome subunit alpha type-7-like [KO:K02731] [EC:3.4.25.1]
29672  Psma5; proteasome subunit alpha type-5 [KO:K02729] [EC:3.4.25.1]
29668  Psma1; proteasome subunit alpha type-1 [KO:K02725] [EC:3.4.25.1]
29670  Psma3; proteasome subunit alpha type-3 [KO:K02727] [EC:3.4.25.1]
29666  Psmb6; proteasome subunit beta type-6 [KO:K02738] [EC:3.4.25.1]
100360846  uncharacterized protein LOC100360846 [KO:K02738] [EC:3.4.25.1]
85492  Psmb7; proteasome subunit beta type-7 [KO:K02739] [EC:3.4.25.1]
29676  Psmb3; proteasome subunit beta type-3 [KO:K02735] [EC:3.4.25.1]
29675  Psmb2; proteasome subunit beta type-2 [KO:K02734] [EC:3.4.25.1]
29425  Psmb5; proteasome subunit beta type-5 [KO:K02737] [EC:3.4.25.1]
94198  Psmb1; proteasome subunit beta type-1 precursor [KO:K02732] [EC:3.4.25.1]
58854  Psmb4; proteasome subunit beta type-4 [KO:K02736] [EC:3.4.25.1]
25581  Psmc2; 26S proteasome regulatory subunit 7 [KO:K03061]
117263  Psmc1; 26S proteasome regulatory subunit 4 [KO:K03062]
117262  Psmc4; 26S proteasome regulatory subunit 6B [KO:K03063]
289990  Psmc6; 26S protease regulatory subunit 10B [KO:K03064]
29677  Psmc3; 26S proteasome regulatory subunit 6A [KO:K03065]
81827  Psmc5; 26S proteasome regulatory subunit 8 [KO:K03066]
287984  Psmd2; 26S proteasome non-ATPase regulatory subunit 2 [KO:K03028]
83806  Psmd1; 26S proteasome non-ATPase regulatory subunit 1 [KO:K03032]
287670  Psmd3; 26S proteasome non-ATPase regulatory subunit 3 [KO:K03033]
161475  Psmd9; 26S proteasome non-ATPase regulatory subunit 9 [KO:K06693]
287772  Psmd12; 26S proteasome non-ATPase regulatory subunit 12 [KO:K03035]
303353  Psmd11; 26S proteasome non-ATPase regulatory subunit 11 [KO:K03036]
289924  Psmd6; 26S proteasome non-ATPase regulatory subunit 6 [KO:K03037]
307821  Psmd7; 26S proteasome non-ATPase regulatory subunit 7 [KO:K03038]
365388  Psmd13; 26S proteasome non-ATPase regulatory subunit 13 [KO:K03039]
83499  Psmd4; 26S proteasome non-ATPase regulatory subunit 4 [KO:K03029]
311078  Psmd14; 26S proteasome non-ATPase regulatory subunit 14 [KO:K03030]
292766  Psmd8; 26S proteasome non-ATPase regulatory subunit 8 [KO:K03031]
65138  Adrm1; proteasomal ubiquitin receptor ADRM1 [KO:K06691]
680532  Sem1; 26S proteasome complex subunit DSS1 [KO:K10881]
156117  Casp12; caspase-12 [KO:K04741] [EC:3.4.22.-]
24598  Nos1; nitric oxide synthase, brain [KO:K13240] [EC:1.14.13.39]
29153  Capn1; calpain-1 catalytic subunit [KO:K01367] [EC:3.4.22.52]
29154  Capn2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
116671  Cdk5r1; cyclin-dependent kinase 5 activator 1 [KO:K11716]
305846  Slc39a2; zinc transporter ZIP2 [KO:K14709]
314637  Slc39a3; zinc transporter ZIP3 [KO:K14709]
361986  Slc39a1; zinc transporter ZIP1 [KO:K14709]
300051  Slc39a4; zinc transporter ZIP4 precursor [KO:K14710]
362812  Slc39a5; zinc transporter ZIP5 precursor [KO:K14711]
291733  Slc39a6; zinc transporter ZIP6 precursor [KO:K14712]
294281  Slc39a7; zinc transporter SLC39A7 precursor [KO:K14713]
295455  Slc39a8; metal cation symporter ZIP8 precursor [KO:K14714]
314275  Slc39a9; zinc transporter ZIP9 [KO:K14715]
363229  Slc39a10; zinc transporter ZIP10 precursor [KO:K14716]
287796  Slc39a11; zinc transporter ZIP11 [KO:K14717]
291328  Slc39a12; zinc transporter ZIP12 [KO:K14718]
295928  Slc39a13; zinc transporter ZIP13 precursor [KO:K14719]
306009  Slc39a14; zinc transporter ZIP14 precursor [KO:K14720]
25715  Slc11a2; natural resistance-associated macrophage protein 2 [KO:K21398]
140908  Cdk5; cyclin-dependent-like kinase 5 [KO:K02090] [EC:2.7.11.22]
84027  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
64026  Casp7; caspase-7 [KO:K04397] [EC:3.4.22.60]
293897  Dkk1; dickkopf-related protein 1 precursor [KO:K02165]
295445  Dkk2; dickkopf-related protein 2 precursor [KO:K02165]
502097  Dkk4; dickkopf-related protein 4 precursor [KO:K02165]
24881  Wnt1; proto-oncogene Wnt-1 precursor [KO:K03209]
116466  Wnt2b; protein Wnt-2b [KO:K00182]
114487  Wnt2; protein Wnt-2 [KO:K00182]
24882  Wnt3; proto-oncogene Wnt-3 [KO:K00312]
303181  Wnt3a; protein Wnt-3a [KO:K00312]
84426  Wnt4; protein Wnt-4 precursor [KO:K00408]
64566  Wnt5a; protein Wnt-5a precursor [KO:K00444]
282582  Wnt5b; protein Wnt-5b precursor [KO:K00444]
316526  Wnt6; protein Wnt-6 precursor [KO:K00445]
114850  Wnt7a; protein Wnt-7a precursor [KO:K00572]
315196  Wnt7b; protein Wnt-7b [KO:K00572]
291678  Wnt8a; protein Wnt-8a precursor [KO:K00714]
293990  Wnt8b; protein Wnt-8b [KO:K00714]
287357  Wnt9a; protein Wnt-9a precursor [KO:K01064]
303586  Wnt9b; protein Wnt-9b precursor [KO:K01064]
315294  Wnt10b; protein Wnt-10b precursor [KO:K01357]
316527  Wnt10a; protein Wnt-10a precursor [KO:K01357]
140584  Wnt11; protein Wnt-11 [KO:K01384]
500047  Wnt16; protein Wnt-16 precursor [KO:K01558]
58868  Fzd1; frizzled-1 precursor [KO:K02432]
100360552  Fzd7; frizzled-7 precursor [KO:K02432]
64512  Fzd2; frizzled-2 precursor [KO:K02235]
266715  Fzd3; frizzled-3 precursor [KO:K02329]
64558  Fzd4; frizzled-4 precursor [KO:K02354]
317674  Fzd5; frizzled-5 precursor [KO:K02375]
364754  Fzd8; frizzled-8 precursor [KO:K02375]
282581  Fzd6; frizzled-6 precursor [KO:K02376]
266608  Fzd9; frizzled-9 precursor [KO:K02842]
363913  Fzd10; frizzled-10 precursor [KO:K02842]
312781  Lrp6; low-density lipoprotein receptor-related protein 6 [KO:K03068]
293649  Lrp5; low-density lipoprotein receptor-related protein 5 precursor [KO:K03068]
58822  Csnk1e; casein kinase I [KO:K08960] [EC:2.7.11.1]
83721  Dvl1; segment polarity protein dishevelled homolog DVL-1 [KO:K02353]
303811  Dvl3; segment polarity protein dishevelled homolog DVL-3 [KO:K02353]
303251  Dvl2; segment polarity protein dishevelled homolog DVL-2 [KO:K02353]
308692  Peg12; paternally expressed 12 [KO:K03069]
103691373  Frat1; proto-oncogene FRAT1 [KO:K03069]
679110  Frat2; GSK-3-binding protein FRAT2 [KO:K03096]
116549  Csnk2a1; casein kinase II subunit alpha [KO:K03097] [EC:2.7.11.1]
307641  Csnk2a2; casein kinase II subunit alpha' [KO:K03097] [EC:2.7.11.1]
81650  Csnk2b; casein kinase II subunit beta [KO:K03115]
79257  Axin1; axin-1 [KO:K02157]
29134  Axin2; axin-2 [KO:K04385]
24205  Apc; adenomatous polyposis coli protein [KO:K02085]
299611  Apc2; adenomatous polyposis coli protein 2 [KO:K02085]
84353  Ctnnb1; catenin beta-1 [KO:K02105]
113927  Csnk1a1; casein kinase I isoform alpha [KO:K08957] [EC:2.7.11.1]
117550  Kif5b; kinesin-1 heavy chain [KO:K10396]
311024  Kif5c; kinesin heavy chain isoform 5C [KO:K10396]
314906  Kif5a; kinesin heavy chain isoform 5A [KO:K10396]
171041  Klc1; kinesin light chain 1 isoform C [KO:K10407]
171549  Klc3; kinesin light chain 3 [KO:K10407]
316226  Klc4; kinesin light chain 4 [KO:K10407]
309159  Klc2; kinesin light chain 2 [KO:K10407]
64158  Tuba1a; tubulin alpha-1A chain [KO:K07374]
291287  Tubal3; tubulin alpha chain-like 3 [KO:K07374]
300218  Tuba1c; tubulin alpha-1C chain [KO:K07374]
316531  Tuba4a; tubulin alpha-4A chain [KO:K07374]
500319  Tuba3a; tubulin alpha-3 chain [KO:K07374]
500363  Tuba3b; tubulin alpha-3 chain [KO:K07374]
500377  Tuba8; tubulin alpha-8 chain [KO:K07374]
500929  Tuba1b; tubulin alpha-1B chain [KO:K07374]
29214  Tubb5; tubulin beta-5 chain [KO:K07375]
246118  Tubb3; tubulin beta-3 chain [KO:K07375]
291081  Tubb2b; tubulin beta-2B chain [KO:K07375]
29213  Tubb4a; tubulin beta-4A chain [KO:K07375]
307351  Tubb6; tubulin beta-6 chain [KO:K07375]
498736  Tubb2a; tubulin beta-2A chain [KO:K07375]
679312  Tubb1; tubulin beta-1 chain isoform X1 [KO:K07375]
296554  Tubb4b; tubulin beta-4B chain [KO:K07375]
81722  Ager; advanced glycosylation end product-specific receptor precursor [KO:K19722]
293621  Hras; GTPase HRas [KO:K02833]
367858  GTPase HRas [KO:K02833]
24525  Kras; GTPase KRas [KO:K07827]
24605  Nras; GTPase NRas [KO:K07828]
64363  Araf; serine/threonine-protein kinase A-Raf isoform 1 [KO:K08845] [EC:2.7.11.1]
114486  Braf; serine/threonine-protein kinase B-raf isoform X6 [KO:K04365] [EC:2.7.11.1]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
58960  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
114243  Nox1; NADPH oxidase 1 [KO:K08008]
66021  Cybb; cytochrome b-245 beta chain [KO:K21421] [EC:1.-.-.-]
85431  Nox4; NADPH oxidase 4 [KO:K21423] [EC:1.6.3.-]
309165  Rela; transcription factor p65 [KO:K04735]
81736  Nfkb1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
24599  Nos2; nitric oxide synthase, inducible [KO:K13241] [EC:1.14.13.39]
29527  Ptgs2; prostaglandin G/H synthase 2 precursor [KO:K11987] [EC:1.14.99.1]
24835  Tnf; tumor necrosis factor [KO:K03156]
24498  Il6; interleukin-6 precursor [KO:K05405]
24493  Il1a; interleukin-1 alpha [KO:K04383]
24494  Il1b; interleukin-1 beta [KO:K04519]
78965  Csf1; macrophage colony-stimulating factor 1 precursor [KO:K05453]
29219  Snca; alpha-synuclein [KO:K04528]
54287  Eif2ak2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
309361  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
84351  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
309295  Ikbkg; NF-kappa-B essential modulator [KO:K07210]
24506  Ins2; insulin-2 preproprotein [KO:K04526]
24505  Ins1; insulin-1 preproprotein [KO:K04526]
24954  Insr; insulin receptor preproprotein [KO:K04527] [EC:2.7.10.1]
25467  Irs1; insulin receptor substrate 1 [KO:K16172]
29376  Irs2; insulin receptor substrate 2 [KO:K07187]
84021  Irs3; insulin receptor substrate 3 [KO:K17445]
315350  Irs4; LOW QUALITY PROTEIN: insulin receptor substrate 4 [KO:K17446]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
56718  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
360827  Ulk1; serine/threonine-protein kinase ULK1 [KO:K21357] [EC:2.7.11.1]
303206  Ulk2; serine/threonine-protein kinase ULK2 [KO:K08269] [EC:2.7.11.1]
300240  Atg101; autophagy-related protein 101 isoform 2 [KO:K19730]
362164  Atg13; autophagy-related protein 13 [KO:K08331]
312927  Rb1cc1; RB1-inducible coiled-coil protein 1 [KO:K17589]
59319  Ambra1; activating molecule in BECN1-regulated autophagy protein 1 [KO:K17985]
114558  Becn1; beclin-1 [KO:K08334]
363131  Pik3r4; phosphoinositide 3-kinase regulatory subunit 4 [KO:K08333] [EC:2.7.11.1]
305831  Atg14; beclin 1-associated autophagy-related key regulator [KO:K17889]
58839  Nrbf2; nuclear receptor-binding factor 2 [KO:K21246]
100363472  nuclear receptor-binding factor 2-like [KO:K21246]
499670  RGD1560263; nuclear receptor-binding factor 2-like [KO:K21246]
65052  Pik3c3; phosphatidylinositol 3-kinase catalytic subunit type 3 [KO:K00914] [EC:2.7.1.137]
689688  Atg2a; autophagy-related protein 2 homolog A [KO:K17906]
288498  Wipi2; WD repeat domain phosphoinositide-interacting protein 2 [KO:K17908]
303630  Wipi1; WD repeat domain phosphoinositide-interacting protein 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
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Dickson DW
  Title
Apoptotic mechanisms in Alzheimer neurofibrillary degeneration: cause or effect?
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J Clin Invest 114:23-7 (2004)
DOI:10.1172/JCI22317
Reference
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Takuma K, Yan SS, Stern DM, Yamada K
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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)
DOI:10.1254/jphs.CPJ04006X
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Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease.
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Trends Neurosci 31:454-63 (2008)
DOI:10.1016/j.tins.2008.06.005
Reference
PMID:9848086
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Possible causes of Alzheimer's disease: amyloid fragments, free radicals, and calcium homeostasis.
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Neurobiol Dis 5:129-41 (1998)
DOI:10.1006/nbdi.1998.0193
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Calcium dysregulation in Alzheimer's disease.
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Neurochem Int 52:621-33 (2008)
DOI:10.1016/j.neuint.2007.10.002
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Kondratskyi A, Kondratska K, Skryma R, Prevarskaya N
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Ion channels in the regulation of apoptosis.
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Biochim Biophys Acta 1848:2532-46 (2015)
DOI:10.1016/j.bbamem.2014.10.030
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Popugaeva E, Pchitskaya E, Bezprozvanny I
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Dysregulation of Intracellular Calcium Signaling in Alzheimer's Disease.
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Antioxid Redox Signal 29:1176-1188 (2018)
DOI:10.1089/ars.2018.7506
Reference
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Tan Y, Deng Y, Qing H
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Calcium channel blockers and Alzheimer's disease.
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Neural Regen Res 7:137-40 (2012)
DOI:10.3969/j.issn.1673-5374.2012.02.010
Reference
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Small DH, Mok SS, Bornstein JC
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Alzheimer's disease and Abeta toxicity: from top to bottom.
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Nat Rev Neurosci 2:595-8 (2001)
DOI:10.1038/35086072
Reference
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Parihar MS, Hemnani T
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Alzheimer's disease pathogenesis and therapeutic interventions.
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J Clin Neurosci 11:456-67 (2004)
DOI:10.1016/j.jocn.2003.12.007
Reference
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Cowburn RF, Popescu BO, Ankarcrona M, Dehvari N, Cedazo-Minguez A
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Presenilin-mediated signal transduction.
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Physiol Behav 92:93-7 (2007)
DOI:10.1016/j.physbeh.2007.05.053
Reference
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Honarnejad K, Herms J
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Presenilins: role in calcium homeostasis.
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Int J Biochem Cell Biol 44:1983-6 (2012)
DOI:10.1016/j.biocel.2012.07.019
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Supnet C, Bezprozvanny I
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Presenilins function in ER calcium leak and Alzheimer's disease pathogenesis.
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Cell Calcium 50:303-9 (2011)
DOI:10.1016/j.ceca.2011.05.013
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Hauptmann S, Keil U, Scherping I, Bonert A, Eckert A, Muller WE
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Mitochondrial dysfunction in sporadic and genetic Alzheimer's disease.
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Exp Gerontol 41:668-73 (2006)
DOI:10.1016/j.exger.2006.03.012
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Chen Y, Liu W, McPhie DL, Hassinger L, Neve RL
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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)
DOI:10.1083/jcb.200304003
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Eckert A, Nisbet R, Grimm A, Gotz J
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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)
DOI:10.1016/j.bbadis.2013.08.013
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Strickland MR, Holtzman DM
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Dr. Jekyll and Mr. Hyde: ApoE explains opposing effects of neuronal LRP1.
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J Clin Invest 129:969-971 (2019)
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Neuronal apoptosis induced by beta-amyloid is mediated by caspase-8.
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Neurobiol Dis 6:440-9 (1999)
DOI:10.1006/nbdi.1999.0268
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Sushma, Mondal AC
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Role of GPCR signaling and calcium dysregulation in Alzheimer's disease.
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Mol Cell Neurosci 101:103414 (2019)
DOI:10.1016/j.mcn.2019.103414
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Sanz-Blasco S, Valero RA, Rodriguez-Crespo I, Villalobos C, Nunez L
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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
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Mattson MP
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ER calcium and Alzheimer's disease: in a state of flux.
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Sci Signal 3:pe10 (2010)
DOI:10.1126/scisignal.3114pe10
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Lee SY, Hwang DY, Kim YK, Lee JW, Shin IC, Oh KW, Lee MK, Lim JS, Yoon DY, Hwang SJ, Hong JT
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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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FASEB J 20:151-3 (2006)
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Disturbed activation of endoplasmic reticulum stress transducers by familial Alzheimer's disease-linked presenilin-1 mutations.
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J Biol Chem 276:43446-54 (2001)
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ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease.
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J Alzheimers Dis 23:335-47 (2011)
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Computational identification of potential multitarget treatments for ameliorating the adverse effects of amyloid-beta on synaptic plasticity.
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Front Neurosci 10:459 (2016)
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Expert Rev Neurother 9:1635-45 (2009)
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Alzheimer's presenilin 1 mutations impair kinesin-based axonal transport.
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Soluble amyloid-beta oligomers as synaptotoxins leading to cognitive impairment in Alzheimer's disease.
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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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  Title
Aberrant insulin signaling in Alzheimer's disease: current knowledge.
  Journal
Front Neurosci 9:204 (2015)
DOI:10.3389/fnins.2015.00204
Reference
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Mt Sinai J Med 77:59-68 (2010)
DOI:10.1002/msj.20161
Related
pathway
rno00190  Oxidative phosphorylation
rno03050  Proteasome
rno04020  Calcium signaling pathway
rno04140  Autophagy - animal
rno04141  Protein processing in endoplasmic reticulum
rno04210  Apoptosis
rno04310  Wnt signaling pathway
rno04910  Insulin signaling pathway
rno04933  AGE-RAGE signaling pathway in diabetic complications
KO pathway
ko05010   
LinkDB

DBGET integrated database retrieval system