PATHWAY: mmu05010 Help
Entry
Name
Alzheimer disease - Mus musculus (house mouse)
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
BRITE hierarchy
Pathway map
Ortholog table
Organism
Mus musculus (house mouse) [GN:
mmu ]
Gene
234664 Nae1; NEDD8 activating enzyme E1 subunit 1 [KO:K04532 ]
11785 Apbb1; amyloid beta precursor protein binding family B member 1 [KO:K04529 ]
66340 Psenen; presenilin enhancer gamma secretase subunit [KO:K06170 ]
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 ]
17762 Mapt; microtubule-associated protein tau [KO:K04380 ]
78330 Ndufv3; NADH:ubiquinone oxidoreductase core subunit V3 [KO:K03944 ]
54405 Ndufa1; NADH:ubiquinone oxidoreductase subunit A1 [KO:K03945 ]
17991 Ndufa2; NADH:ubiquinone oxidoreductase subunit A2 [KO:K03946 ]
66091 Ndufa3; NADH:ubiquinone oxidoreductase subunit A3 [KO:K03947 ]
17992 Ndufa4; Ndufa4, mitochondrial complex associated [KO:K03948 ]
407790 Ndufa4l2; Ndufa4, mitochondrial complex associated like 2 [KO:K03948 ]
68202 Ndufa5; NADH:ubiquinone oxidoreductase subunit A5 [KO:K03949 ]
67130 Ndufa6; NADH:ubiquinone oxidoreductase subunit A6 [KO:K03950 ]
66416 Ndufa7; NADH:ubiquinone oxidoreductase subunit A7 [KO:K03951 ]
68375 Ndufa8; NADH:ubiquinone oxidoreductase subunit A8 [KO:K03952 ]
66108 Ndufa9; NADH:ubiquinone oxidoreductase subunit A9 [KO:K03953 ]
67273 Ndufa10; NADH:ubiquinone oxidoreductase subunit A10 [KO:K03954 ]
70316 Ndufab1; NADH:ubiquinone oxidoreductase subunit AB1 [KO:K03955 ]
102634451 Ndufab1-ps; NADH:ubiquinone oxidoreductase subunit AB1b [KO:K03955 ]
69875 Ndufa11; NADH:ubiquinone oxidoreductase subunit A11 [KO:K03956 ]
66414 Ndufa12; NADH:ubiquinone oxidoreductase subunit A12 [KO:K11352 ]
67184 Ndufa13; NADH:ubiquinone oxidoreductase subunit A13 [KO:K11353 ]
68198 Ndufb2; NADH:ubiquinone oxidoreductase subunit B2 [KO:K03958 ]
66495 Ndufb3; NADH:ubiquinone oxidoreductase subunit B3 [KO:K03959 ]
68194 Ndufb4; NADH:ubiquinone oxidoreductase subunit B4 [KO:K03960 ]
66046 Ndufb5; NADH:ubiquinone oxidoreductase subunit B5 [KO:K03961 ]
230075 Ndufb6; NADH:ubiquinone oxidoreductase subunit B6 [KO:K03962 ]
66916 Ndufb7; NADH:ubiquinone oxidoreductase subunit B7 [KO:K03963 ]
67264 Ndufb8; NADH:ubiquinone oxidoreductase subunit B8 [KO:K03964 ]
66218 Ndufb9; NADH:ubiquinone oxidoreductase subunit B9 [KO:K03965 ]
68342 Ndufb10; NADH:ubiquinone oxidoreductase subunit B10 [KO:K03966 ]
104130 Ndufb11; NADH:ubiquinone oxidoreductase subunit B11 [KO:K11351 ]
17993 Ndufs4; NADH:ubiquinone oxidoreductase core subunit S4 [KO:K03937 ]
595136 Ndufs5; NADH:ubiquinone oxidoreductase core subunit S5 [KO:K03938 ]
407785 Ndufs6; NADH:ubiquinone oxidoreductase core subunit S6 [KO:K03939 ]
623286 Ndufs6b; NADH:ubiquinone oxidoreductase subunit S6B [KO:K03939 ]
66377 Ndufc1; NADH:ubiquinone oxidoreductase subunit C1 [KO:K03967 ]
68197 Ndufc2; NADH:ubiquinone oxidoreductase subunit C2 [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:7.1.1.8 ]
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 ]
17709 COX2; cytochrome c oxidase subunit II [KO:K02261 ]
12857 Cox4i1; cytochrome c oxidase subunit 4I1 [KO:K02263 ]
84682 Cox4i2; cytochrome c oxidase subunit 4I2 [KO:K02263 ]
12858 Cox5a; cytochrome c oxidase subunit 5A [KO:K02264 ]
12859 Cox5b; cytochrome c oxidase subunit 5B [KO:K02265 ]
12861 Cox6a1; cytochrome c oxidase subunit 6A1 [KO:K02266 ]
12862 Cox6a2; cytochrome c oxidase subunit 6A2 [KO:K02266 ]
110323 Cox6b1; cytochrome c oxidase, subunit 6B1 [KO:K02267 ]
12864 Cox6c; cytochrome c oxidase subunit 6C [KO:K02268 ]
12866 Cox7a2; cytochrome c oxidase subunit 7A2 [KO:K02270 ]
12865 Cox7a1; cytochrome c oxidase subunit 7A1 [KO:K02270 ]
20463 Cox7a2l; cytochrome c oxidase subunit 7A2 like [KO:K02270 ]
66142 Cox7b; cytochrome c oxidase subunit 7B [KO:K02271 ]
78174 Cox7b2; cytochrome c oxidase subunit 7B2 [KO:K02271 ]
12867 Cox7c; cytochrome c oxidase subunit 7C [KO:K02272 ]
12868 Cox8a; cytochrome c oxidase subunit 8A [KO:K02273 ]
12869 Cox8b; cytochrome c oxidase subunit 8B [KO:K02273 ]
75483 Cox8c; cytochrome c oxidase subunit 8C [KO:K02273 ]
11946 Atp5f1a; ATP synthase F1 subunit alpha [KO:K02132 ]
11949 Atp5f1c; ATP synthase F1 subunit gamma [KO:K02136 ]
66043 Atp5f1d; ATP synthase F1 subunit delta [KO:K02134 ]
67126 Atp5f1e; ATP synthase F1 subunit epsilon [KO:K02135 ]
11950 Atp5pb; ATP synthase peripheral stalk-membrane subunit b [KO:K02127 ]
11951 Atp5mc1; ATP synthase membrane subunit c locus 1 [KO:K02128 ]
67942 Atp5mc2; ATP synthase membrane subunit c locus 2 [KO:K02128 ]
228033 Atp5mc3; ATP synthase membrane subunit c locus 3 [KO:K02128 ]
71679 Atp5pd; ATP synthase peripheral stalk subunit d [KO:K02138 ]
28080 Atp5po; ATP synthase peripheral stalk subunit OSCP [KO:K02137 ]
11957 Atp5pf; ATP synthase peripheral stalk subunit F6 [KO:K02131 ]
22333 Vdac1; voltage-dependent anion channel 1 [KO:K05862 ]
22334 Vdac2; voltage-dependent anion channel 2 [KO:K15040 ]
22335 Vdac3; voltage-dependent anion channel 3 [KO:K15041 ]
11739 Slc25a4; solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 4 [KO:K05863 ]
11740 Slc25a5; solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 5 [KO:K05863 ]
73333 Slc25a31; solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 31 [KO:K05863 ]
16971 Lrp1; low density lipoprotein receptor-related protein 1 [KO:K04550 ]
21937 Tnfrsf1a; tumor necrosis factor receptor superfamily, member 1a [KO:K03158 ]
14082 Fadd; Fas associated via death domain [KO:K02373 ]
12122 Bid; BH3 interacting domain death agonist [KO:K04726 ]
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 ]
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 ]
11783 Apaf1; apoptotic peptidase activating factor 1 [KO:K02084 ]
12669 Chrm1; cholinergic receptor, muscarinic 1, CNS [KO:K04129 ]
12671 Chrm3; cholinergic receptor, muscarinic 3, cardiac [KO:K04131 ]
213788 Chrm5; cholinergic receptor, muscarinic 5 [KO:K04133 ]
14682 Gnaq; guanine nucleotide binding protein, alpha q polypeptide [KO:K04634 ]
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 ]
11441 Chrna7; cholinergic receptor, nicotinic, alpha polypeptide 7 [KO:K04809 ]
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:7.2.2.10 ]
11938 Atp2a2; ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 [KO:K05853 ] [EC:7.2.2.10 ]
13198 Ddit3; DNA-damage inducible transcript 3 [KO:K04452 ]
13666 Eif2ak3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860 ] [EC:2.7.11.1 ]
13665 Eif2s1; eukaryotic translation initiation factor 2, subunit 1 alpha [KO:K03237 ]
11911 Atf4; activating transcription factor 4 [KO:K04374 ]
19181 Psmc2; proteasome (prosome, macropain) 26S subunit, ATPase 2 [KO:K03061 ]
19179 Psmc1; protease (prosome, macropain) 26S subunit, ATPase 1 [KO:K03062 ]
23996 Psmc4; proteasome (prosome, macropain) 26S subunit, ATPase, 4 [KO:K03063 ]
67089 Psmc6; proteasome (prosome, macropain) 26S subunit, ATPase, 6 [KO:K03064 ]
19182 Psmc3; proteasome (prosome, macropain) 26S subunit, ATPase 3 [KO:K03065 ]
19184 Psmc5; protease (prosome, macropain) 26S subunit, ATPase 5 [KO:K03066 ]
21762 Psmd2; proteasome (prosome, macropain) 26S subunit, non-ATPase, 2 [KO:K03028 ]
70247 Psmd1; proteasome (prosome, macropain) 26S subunit, non-ATPase, 1 [KO:K03032 ]
22123 Psmd3; proteasome (prosome, macropain) 26S subunit, non-ATPase, 3 [KO:K03033 ]
67151 Psmd9; proteasome (prosome, macropain) 26S subunit, non-ATPase, 9 [KO:K06693 ]
66997 Psmd12; proteasome (prosome, macropain) 26S subunit, non-ATPase, 12 [KO:K03035 ]
69077 Psmd11; proteasome (prosome, macropain) 26S subunit, non-ATPase, 11 [KO:K03036 ]
66413 Psmd6; proteasome (prosome, macropain) 26S subunit, non-ATPase, 6 [KO:K03037 ]
17463 Psmd7; proteasome (prosome, macropain) 26S subunit, non-ATPase, 7 [KO:K03038 ]
23997 Psmd13; proteasome (prosome, macropain) 26S subunit, non-ATPase, 13 [KO:K03039 ]
19185 Psmd4; proteasome (prosome, macropain) 26S subunit, non-ATPase, 4 [KO:K03029 ]
59029 Psmd14; proteasome (prosome, macropain) 26S subunit, non-ATPase, 14 [KO:K03030 ]
57296 Psmd8; proteasome (prosome, macropain) 26S subunit, non-ATPase, 8 [KO:K03031 ]
56436 Adrm1; adhesion regulating molecule 1 26S proteasome ubiquitin receptor [KO:K06691 ]
20422 Sem1; SEM1, 26S proteasome complex subunit [KO:K10881 ]
12569 Cdk5r1; cyclin dependent kinase 5, regulatory subunit 1 [KO:K11716 ]
214922 Slc39a2; solute carrier family 39 (zinc transporter), member 2 [KO:K14709 ]
106947 Slc39a3; solute carrier family 39 (zinc transporter), member 3 [KO:K14709 ]
30791 Slc39a1; solute carrier family 39 (zinc transporter), member 1 [KO:K14709 ]
72027 Slc39a4; solute carrier family 39 (zinc transporter), member 4 [KO:K14710 ]
72002 Slc39a5; solute carrier family 39 (metal ion transporter), member 5 [KO:K14711 ]
106957 Slc39a6; solute carrier family 39 (metal ion transporter), member 6 [KO:K14712 ]
14977 Slc39a7; solute carrier family 39 (zinc transporter), member 7 [KO:K14713 ]
67547 Slc39a8; solute carrier family 39 (metal ion transporter), member 8 [KO:K14714 ]
328133 Slc39a9; solute carrier family 39 (zinc transporter), member 9 [KO:K14715 ]
227059 Slc39a10; solute carrier family 39 (zinc transporter), member 10 [KO:K14716 ]
69806 Slc39a11; solute carrier family 39 (metal ion transporter), member 11 [KO:K14717 ]
277468 Slc39a12; solute carrier family 39 (zinc transporter), member 12 [KO:K14718 ]
68427 Slc39a13; solute carrier family 39 (metal ion transporter), member 13 [KO:K14719 ]
213053 Slc39a14; solute carrier family 39 (zinc transporter), member 14 [KO:K14720 ]
18174 Slc11a2; solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2 [KO:K21398 ]
13380 Dkk1; dickkopf WNT signaling pathway inhibitor 1 [KO:K02165 ]
56811 Dkk2; dickkopf WNT signaling pathway inhibitor 2 [KO:K02165 ]
234130 Dkk4; dickkopf WNT signaling pathway inhibitor 4 [KO:K02165 ]
22408 Wnt1; wingless-type MMTV integration site family, member 1 [KO:K03209 ]
22413 Wnt2; wingless-type MMTV integration site family, member 2 [KO:K00182 ]
22414 Wnt2b; wingless-type MMTV integration site family, member 2B [KO:K00182 ]
22415 Wnt3; wingless-type MMTV integration site family, member 3 [KO:K00312 ]
22416 Wnt3a; wingless-type MMTV integration site family, member 3A [KO:K00312 ]
22417 Wnt4; wingless-type MMTV integration site family, member 4 [KO:K00408 ]
22418 Wnt5a; wingless-type MMTV integration site family, member 5A [KO:K00444 ]
22419 Wnt5b; wingless-type MMTV integration site family, member 5B [KO:K00444 ]
22420 Wnt6; wingless-type MMTV integration site family, member 6 [KO:K00445 ]
22421 Wnt7a; wingless-type MMTV integration site family, member 7A [KO:K00572 ]
22422 Wnt7b; wingless-type MMTV integration site family, member 7B [KO:K00572 ]
20890 Wnt8a; wingless-type MMTV integration site family, member 8A [KO:K00714 ]
22423 Wnt8b; wingless-type MMTV integration site family, member 8B [KO:K00714 ]
216795 Wnt9a; wingless-type MMTV integration site family, member 9A [KO:K01064 ]
22412 Wnt9b; wingless-type MMTV integration site family, member 9B [KO:K01064 ]
22410 Wnt10b; wingless-type MMTV integration site family, member 10B [KO:K01357 ]
22409 Wnt10a; wingless-type MMTV integration site family, member 10A [KO:K01357 ]
22411 Wnt11; wingless-type MMTV integration site family, member 11 [KO:K01384 ]
93735 Wnt16; wingless-type MMTV integration site family, member 16 [KO:K01558 ]
16973 Lrp5; low density lipoprotein receptor-related protein 5 [KO:K03068 ]
16974 Lrp6; low density lipoprotein receptor-related protein 6 [KO:K03068 ]
13544 Dvl3; dishevelled segment polarity protein 3 [KO:K02353 ]
13542 Dvl1; dishevelled segment polarity protein 1 [KO:K02353 ]
13543 Dvl2; dishevelled segment polarity protein 2 [KO:K02353 ]
14296 Frat1; frequently rearranged in advanced T cell lymphomas [KO:K03069 ]
212398 Frat2; frequently rearranged in advanced T cell lymphomas 2 [KO:K03096 ]
13001 Csnk2b; casein kinase 2, beta polypeptide [KO:K03115 ]
11789 Apc; APC, WNT signaling pathway regulator [KO:K02085 ]
23805 Apc2; APC regulator of WNT signaling pathway 2 [KO:K02085 ]
11596 Ager; advanced glycosylation end product-specific receptor [KO:K19722 ]
15461 Hras; Harvey rat sarcoma virus oncogene [KO:K02833 ]
16653 Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827 ]
13058 Cybb; cytochrome b-245, beta polypeptide [KO:K21421 ] [EC:1.-.-.-]
19697 Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735 ]
18033 Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580 ]
12977 Csf1; colony stimulating factor 1 (macrophage) [KO:K05453 ]
19106 Eif2ak2; eukaryotic translation initiation factor 2-alpha kinase 2 [KO:K16195 ] [EC:2.7.11.1 ]
16151 Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210 ]
18709 Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
18708 Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
18710 Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
18706 Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
18707 Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
74769 Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
52639 Wipi1; WD repeat domain, phosphoinositide interacting 1 [KO:K17908 ]
74781 Wipi2; WD repeat domain, phosphoinositide interacting 2 [KO:K17908 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
C04549 1-Phosphatidyl-1D-myo-inositol 3-phosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
C16514 Amyloid beta protein 40
C16515 Amyloid beta protein 42
C21011 [Protein]-N(epsilon)-(carboxymethyl)lysine
C21012 [Protein]-N(epsilon)-(carboxyethyl)lysine
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Reference
Authors
Funderburk SF, Marcellino BK, Yue Z
Title
Cell "self-eating" (autophagy) mechanism in Alzheimer's disease.
Journal
Related pathway
mmu04141 Protein processing in endoplasmic reticulum
mmu04933 AGE-RAGE signaling pathway in diabetic complications
KO pathway
LinkDB
All DBs