KEGG   PATHWAY: mmu05010Help
Entry
mmu05010                    Pathway                                

Name
Alzheimer's disease - Mus musculus (mouse)
Description
Alzheimer's 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. The extracellular Abeta oligomers may activate caspases through activation of cell surface death receptors. Alternatively, intracellular Abeta may contribute to pathology by facilitating tau hyper-phosphorylation, disrupting mitochondria function, and triggering calcium dysfunction. 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. FAD-linked PS1 mutation downregulates the unfolded protein response and leads to vulnerability to ER stress.
Class
Human Diseases; Neurodegenerative diseases
BRITE hierarchy
Pathway map
Alzheimer's disease
mmu05010

All organismsOrtholog table
Organism
Mus musculus (mouse) [GN:mmu]
Gene
11487  
Adam10; a disintegrin and metallopeptidase domain 10 [KO:K06704] [EC:3.4.24.81]
11491  
Adam17; a disintegrin and metallopeptidase domain 17 [KO:K06059] [EC:3.4.24.86]
11820  
App; amyloid beta (A4) precursor protein [KO:K04520]
234664  
Nae1; NEDD8 activating enzyme E1 subunit 1 [KO:K04532]
11785  
Apbb1; amyloid beta (A4) precursor protein-binding, family B, member 1 [KO:K04529]
14433  
Gapdh; glyceraldehyde-3-phosphate dehydrogenase [KO:K00134] [EC:1.2.1.12]
Gapdh-ps15; glyceraldehyde-3-phosphate dehydrogenase, pseudogene 15 [KO:K00134] [EC:1.2.1.12]
23821  
Bace1; beta-site APP cleaving enzyme 1 [KO:K04521] [EC:3.4.23.46]
56175  
Bace2; beta-site APP-cleaving enzyme 2 [KO:K07747] [EC:3.4.23.45]
66340  
Psenen; presenilin enhancer gamma secretase subunit [KO:K06170]
19164  
Psen1; presenilin 1 [KO:K04505] [EC:3.4.23.-]
19165  
Psen2; presenilin 2 [KO:K04522] [EC:3.4.23.-]
59287  
Ncstn; nicastrin [KO:K06171]
226548  
Aph1a; aph1 homolog A, gamma secretase subunit [KO:K06172]
68318  
Aph1c; aph1 homolog C, gamma secretase subunit [KO:K06172]
208117  
Aph1b; aph1 homolog B, gamma secretase subunit [KO:K06172]
15925  
Ide; insulin degrading enzyme [KO:K01408] [EC:3.4.24.56]
17380  
Mme; membrane metallo endopeptidase [KO:K01389] [EC:3.4.24.11]
17995  
Ndufv1; NADH dehydrogenase (ubiquinone) flavoprotein 1 [KO:K03942] [EC:1.6.99.3 1.6.5.3]
72900  
Ndufv2; NADH dehydrogenase (ubiquinone) flavoprotein 2 [KO:K03943] [EC:1.6.99.3 1.6.5.3]
78330  
Ndufv3; NADH dehydrogenase (ubiquinone) flavoprotein 3 [KO:K03944]
54405  
Ndufa1; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 1 [KO:K03945]
17991  
Ndufa2; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 2 [KO:K03946]
66091  
Ndufa3; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 3 [KO:K03947]
17992  
Ndufa4; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4 [KO:K03948]
407790  
Ndufa4l2; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 [KO:K03948]
68202  
Ndufa5; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 5 [KO:K03949]
67130  
Ndufa6; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 6 (B14) [KO:K03950]
66416  
Ndufa7; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 7 (B14.5a) [KO:K03951]
68375  
Ndufa8; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 8 [KO:K03952]
66108  
Ndufa9; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 9 [KO:K03953]
67273  
Ndufa10; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 10 [KO:K03954]
70316  
Ndufab1; NADH dehydrogenase (ubiquinone) 1, alpha/beta subcomplex, 1 [KO:K03955]
239760  
Gm4943; predicted pseudogene 4943 [KO:K03956]
69875  
Ndufa11; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 11 [KO:K03956]
66414  
Ndufa12; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 12 [KO:K11352]
67184  
Ndufa13; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 13 [KO:K11353]
68198  
Ndufb2; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 2 [KO:K03958]
66495  
Ndufb3; NADH dehydrogenase (ubiquinone) 1 beta subcomplex 3 [KO:K03959]
68194  
Ndufb4; NADH dehydrogenase (ubiquinone) 1 beta subcomplex 4 [KO:K03960]
Gm3873; predicted gene 3873 [KO:K03960]
Gm3244; predicted pseudogene 3244 [KO:K03960]
66046  
Ndufb5; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 5 [KO:K03961]
230075  
Ndufb6; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 6 [KO:K03962]
66916  
Ndufb7; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 7 [KO:K03963]
67264  
Ndufb8; NADH dehydrogenase (ubiquinone) 1 beta subcomplex 8 [KO:K03964]
66218  
Ndufb9; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 9 [KO:K03965]
68342  
Ndufb10; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 10 [KO:K03966]
104130  
Ndufb11; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 11 [KO:K11351]
227197  
Ndufs1; NADH dehydrogenase (ubiquinone) Fe-S protein 1 [KO:K03934] [EC:1.6.99.3 1.6.5.3]
226646  
Ndufs2; NADH dehydrogenase (ubiquinone) Fe-S protein 2 [KO:K03935] [EC:1.6.99.3 1.6.5.3]
68349  
Ndufs3; NADH dehydrogenase (ubiquinone) Fe-S protein 3 [KO:K03936] [EC:1.6.99.3 1.6.5.3]
17993  
Ndufs4; NADH dehydrogenase (ubiquinone) Fe-S protein 4 [KO:K03937]
595136  
Ndufs5; NADH dehydrogenase (ubiquinone) Fe-S protein 5 [KO:K03938]
407785  
Ndufs6; NADH dehydrogenase (ubiquinone) Fe-S protein 6 [KO:K03939]
75406  
Ndufs7; NADH dehydrogenase (ubiquinone) Fe-S protein 7 [KO:K03940] [EC:1.6.99.3 1.6.5.3]
225887  
Ndufs8; NADH dehydrogenase (ubiquinone) Fe-S protein 8 [KO:K03941] [EC:1.6.99.3 1.6.5.3]
66377  
Ndufc1; NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 1 [KO:K03967]
68197  
Ndufc2; NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 2 [KO:K03968]
66945  
Sdha; succinate dehydrogenase complex, subunit A, flavoprotein (Fp) [KO:K00234] [EC:1.3.5.1]
67680  
Sdhb; succinate dehydrogenase complex, subunit B, iron sulfur (Ip) [KO:K00235] [EC:1.3.5.1]
66052  
Sdhc; succinate dehydrogenase complex, subunit C, integral membrane protein [KO:K00236]
66925  
Sdhd; succinate dehydrogenase complex, subunit D, integral membrane protein [KO:K00237]
66694  
Uqcrfs1; ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 [KO:K00411] [EC:1.10.2.2]
17711  
CYTB; cytochrome b [KO:K00412]
66445  
Cyc1; cytochrome c-1 [KO:K00413]
22273  
Uqcrc1; ubiquinol-cytochrome c reductase core protein 1 [KO:K00414]
67003  
Uqcrc2; ubiquinol cytochrome c reductase core protein 2 [KO:K00415]
66576  
Uqcrh; ubiquinol-cytochrome c reductase hinge protein [KO:K00416]
67530  
Uqcrb; ubiquinol-cytochrome c reductase binding protein [KO:K00417]
22272  
Uqcrq; ubiquinol-cytochrome c reductase, complex III subunit VII [KO:K00418]
66152  
Uqcr10; ubiquinol-cytochrome c reductase, complex III subunit X [KO:K00419]
66594  
Uqcr11; ubiquinol-cytochrome c reductase, complex III subunit XI [KO:K00420]
17710  
COX3; cytochrome c oxidase subunit III [KO:K02262]
17708  
COX1; cytochrome c oxidase subunit I [KO:K02256] [EC:1.9.3.1]
17709  
COX2; cytochrome c oxidase subunit II [KO:K02261]
12857  
Cox4i1; cytochrome c oxidase subunit IV isoform 1 [KO:K02263]
84682  
Cox4i2; cytochrome c oxidase subunit IV isoform 2 [KO:K02263]
12858  
Cox5a; cytochrome c oxidase subunit Va [KO:K02264]
12859  
Cox5b; cytochrome c oxidase subunit Vb [KO:K02265]
12861  
Cox6a1; cytochrome c oxidase subunit VIa polypeptide 1 [KO:K02266]
12862  
Cox6a2; cytochrome c oxidase subunit VIa polypeptide 2 [KO:K02266]
110323  
Cox6b1; cytochrome c oxidase, subunit VIb polypeptide 1 [KO:K02267]
333182  
Cox6b2; cytochrome c oxidase subunit VIb polypeptide 2 [KO:K02267]
12864  
Cox6c; cytochrome c oxidase subunit VIc [KO:K02268]
12866  
Cox7a2; cytochrome c oxidase subunit VIIa 2 [KO:K02270]
12865  
Cox7a1; cytochrome c oxidase subunit VIIa 1 [KO:K02270]
20463  
Cox7a2l; cytochrome c oxidase subunit VIIa polypeptide 2-like [KO:K02270]
66142  
Cox7b; cytochrome c oxidase subunit VIIb [KO:K02271]
78174  
Cox7b2; cytochrome c oxidase subunit VIIb2 [KO:K02271]
12867  
Cox7c; cytochrome c oxidase subunit VIIc [KO:K02272]
12868  
Cox8a; cytochrome c oxidase subunit VIIIa [KO:K02273]
12869  
Cox8b; cytochrome c oxidase subunit VIIIb [KO:K02273]
75483  
Cox8c; cytochrome c oxidase subunit VIIIc [KO:K02273]
11946  
Atp5a1; ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1 [KO:K02132]
11947  
Atp5b; ATP synthase, H+ transporting mitochondrial F1 complex, beta subunit [KO:K02133] [EC:3.6.3.14]
11949  
Atp5c1; ATP synthase, H+ transporting, mitochondrial F1 complex, gamma polypeptide 1 [KO:K02136]
66043  
Atp5d; ATP synthase, H+ transporting, mitochondrial F1 complex, delta subunit [KO:K02134]
67126  
Atp5e; ATP synthase, H+ transporting, mitochondrial F1 complex, epsilon subunit [KO:K02135]
17705  
ATP6; ATP synthase F0 subunit 6 [KO:K02126]
11950  
Atp5f1; ATP synthase, H+ transporting, mitochondrial F0 complex, subunit B1 [KO:K02127]
11951  
Atp5g1; ATP synthase, H+ transporting, mitochondrial F0 complex, subunit C1 (subunit 9) [KO:K02128]
67942  
Atp5g2; ATP synthase, H+ transporting, mitochondrial F0 complex, subunit C2 (subunit 9) [KO:K02128]
228033  
Atp5g3; ATP synthase, H+ transporting, mitochondrial F0 complex, subunit C3 (subunit 9) [KO:K02128]
71679  
Atp5h; ATP synthase, H+ transporting, mitochondrial F0 complex, subunit D [KO:K02138]
28080  
Atp5o; ATP synthase, H+ transporting, mitochondrial F1 complex, O subunit [KO:K02137]
11957  
Atp5j; ATP synthase, H+ transporting, mitochondrial F0 complex, subunit F [KO:K02131]
17706  
ATP8; ATP synthase F0 subunit 8 [KO:K02125]
15108  
Hsd17b10; hydroxysteroid (17-beta) dehydrogenase 10 [KO:K08683] [EC:1.1.1.178 1.1.1.35]
16956  
Lpl; lipoprotein lipase [KO:K01059] [EC:3.1.1.34]
11816  
Apoe; apolipoprotein E [KO:K04524]
16971  
Lrp1; low density lipoprotein receptor-related protein 1 [KO:K04550]
14102  
Fas; Fas (TNF receptor superfamily member 6) [KO:K04390]
21937  
Tnfrsf1a; tumor necrosis factor receptor superfamily, member 1a [KO:K03158]
14082  
Fadd; Fas (TNFRSF6)-associated via death domain [KO:K02373]
12370  
Casp8; caspase 8 [KO:K04398] [EC:3.4.22.61]
12122  
Bid; BH3 interacting domain death agonist [KO:K04726]
12313  
Calm1; calmodulin 1 [KO:K02183]
80796  
Calm4; calmodulin 4 [KO:K02183]
12315  
Calm3; calmodulin 3 [KO:K02183]
12314  
Calm2; calmodulin 2 [KO:K02183]
70405  
Calml3; calmodulin-like 3 [KO:K02183]
494124  
Calm5; calmodulin 5 [KO:K02183]
19057  
Ppp3cc; protein phosphatase 3, catalytic subunit, gamma isoform [KO:K04348] [EC:3.1.3.16]
19055  
Ppp3ca; protein phosphatase 3, catalytic subunit, alpha isoform [KO:K04348] [EC:3.1.3.16]
19056  
Ppp3cb; protein phosphatase 3, catalytic subunit, beta isoform [KO:K04348] [EC:3.1.3.16]
19058  
Ppp3r1; protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type I) [KO:K06268]
19059  
Ppp3r2; protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type II) [KO:K06268]
12015  
Bad; BCL2-associated agonist of cell death [KO:K02158]
13063  
Cycs; cytochrome c, somatic [KO:K08738]
13067  
Cyct; cytochrome c, testis [KO:K08738]
11783  
Apaf1; apoptotic peptidase activating factor 1 [KO:K02084]
12371  
Casp9; caspase 9 [KO:K04399] [EC:3.4.22.62]
12367  
Casp3; caspase 3 [KO:K02187] [EC:3.4.22.56]
14682  
Gnaq; guanine nucleotide binding protein, alpha q polypeptide [KO:K04634]
18795  
Plcb1; phospholipase C, beta 1 [KO:K05858] [EC:3.1.4.11]
18797  
Plcb3; phospholipase C, beta 3 [KO:K05858] [EC:3.1.4.11]
18798  
Plcb4; phospholipase C, beta 4 [KO:K05858] [EC:3.1.4.11]
18796  
Plcb2; phospholipase C, beta 2 [KO:K05858] [EC:3.1.4.11]
14810  
Grin1; glutamate receptor, ionotropic, NMDA1 (zeta 1) [KO:K05208]
14811  
Grin2a; glutamate receptor, ionotropic, NMDA2A (epsilon 1) [KO:K05209]
14812  
Grin2b; glutamate receptor, ionotropic, NMDA2B (epsilon 2) [KO:K05210]
14813  
Grin2c; glutamate receptor, ionotropic, NMDA2C (epsilon 3) [KO:K05211]
14814  
Grin2d; glutamate receptor, ionotropic, NMDA2D (epsilon 4) [KO:K05212]
12288  
Cacna1c; calcium channel, voltage-dependent, L type, alpha 1C subunit [KO:K04850]
12289  
Cacna1d; calcium channel, voltage-dependent, L type, alpha 1D subunit [KO:K04851]
54652  
Cacna1f; calcium channel, voltage-dependent, alpha 1F subunit [KO:K04853]
12292  
Cacna1s; calcium channel, voltage-dependent, L type, alpha 1S subunit [KO:K04857]
26413  
Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  
Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
20192  
Ryr3; ryanodine receptor 3 [KO:K04963]
16438  
Itpr1; inositol 1,4,5-trisphosphate receptor 1 [KO:K04958]
16439  
Itpr2; inositol 1,4,5-triphosphate receptor 2 [KO:K04959]
16440  
Itpr3; inositol 1,4,5-triphosphate receptor 3 [KO:K04960]
11937  
Atp2a1; ATPase, Ca++ transporting, cardiac muscle, fast twitch 1 [KO:K05853] [EC:3.6.3.8]
11938  
Atp2a2; ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 [KO:K05853] [EC:3.6.3.8]
53313  
Atp2a3; ATPase, Ca++ transporting, ubiquitous [KO:K05853] [EC:3.6.3.8]
226641  
Atf6; activating transcription factor 6 [KO:K09054]
78943  
Ern1; endoplasmic reticulum (ER) to nucleus signalling 1 [KO:K08852] [EC:3.1.26.- 2.7.11.1]
13666  
Eif2ak3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
12364  
Casp12; caspase 12 [KO:K04741] [EC:3.4.22.-]
18125  
Nos1; nitric oxide synthase 1, neuronal [KO:K13240] [EC:1.14.13.39]
12333  
Capn1; calpain 1 [KO:K01367] [EC:3.4.22.52]
12334  
Capn2; calpain 2 [KO:K03853] [EC:3.4.22.53]
12569  
Cdk5r1; cyclin-dependent kinase 5, regulatory subunit 1 (p35) [KO:K11716]
12568  
Cdk5; cyclin-dependent kinase 5 [KO:K02090] [EC:2.7.11.22]
17762  
Mapt; microtubule-associated protein tau [KO:K04380]
56637  
Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
12369  
Casp7; caspase 7 [KO:K04397] [EC:3.4.22.60]
20617  
Snca; synuclein, alpha [KO:K04528]
21926  
Tnf; tumor necrosis factor [KO:K03156]
16176  
Il1b; interleukin 1 beta [KO:K04519]
 
 
 
 
 
Compound
C00027  
Hydrogen peroxide
C00070  
Copper
C00076  
Calcium cation
C00533  
Nitric oxide
C01245  
D-myo-Inositol 1,4,5-trisphosphate
C14818  
Fe2+
C16845  
Peroxynitrite
Reference
  Authors
Dickson DW
  Title
Apoptotic mechanisms in Alzheimer neurofibrillary degeneration: cause or effect?
  Journal
J Clin Invest 114:23-7 (2004)
Reference
  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)
Reference
  Authors
Bezprozvanny I, Mattson MP
  Title
Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease.
  Journal
Trends Neurosci 31:454-63 (2008)
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)
Reference
  Authors
Bojarski L, Herms J, Kuznicki J
  Title
Calcium dysregulation in Alzheimer's disease.
  Journal
Neurochem Int 52:621-33 (2008)
Reference
  Authors
Katayama T, Imaizumi K, Manabe T, Hitomi J, Kudo T, Tohyama M
  Title
Induction of neuronal death by ER stress in Alzheimer's disease.
  Journal
J Chem Neuroanat 28:67-78 (2004)
Reference
  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)
Reference
  Authors
Mattson MP
  Title
Pathways towards and away from Alzheimer's disease.
  Journal
Nature 430:631-9 (2004)
Reference
  Authors
Parihar MS, Hemnani T
  Title
Alzheimer's disease pathogenesis and therapeutic interventions.
  Journal
J Clin Neurosci 11:456-67 (2004)
Reference
  Authors
Cowburn RF, Popescu BO, Ankarcrona M, Dehvari N, Cedazo-Minguez A
  Title
Presenilin-mediated signal transduction.
  Journal
Physiol Behav 92:93-7 (2007)
Reference
  Authors
Shen Y, He P, Zhong Z, McAllister C, Lindholm K
  Title
Distinct destructive signal pathways of neuronal death in Alzheimer's disease.
  Journal
Trends Mol Med 12:574-9 (2006)
Reference
  Authors
Reese LC, Zhang W, Dineley KT, Kayed R, Taglialatela G
  Title
Selective induction of calcineurin activity and signaling by oligomeric amyloid beta.
  Journal
Aging Cell 7:824-35 (2008)
Reference
  Authors
Lee MS, Kwon YT, Li M, Peng J, Friedlander RM, Tsai LH
  Title
Neurotoxicity induces cleavage of p35 to p25 by calpain.
  Journal
Nature 405:360-4 (2000)
Reference
  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)
Reference
  Authors
Avila J
  Title
Tau phosphorylation and aggregation in Alzheimer's disease pathology.
  Journal
FEBS Lett 580:2922-7 (2006)
Reference
  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)
Reference
  Authors
Gandy S
  Title
The role of cerebral amyloid beta accumulation in common forms of Alzheimer disease.
  Journal
J Clin Invest 115:1121-9 (2005)
KO pathway
 

DBGET integrated database retrieval system