KEGG   PATHWAY: mmu05012Help
Entry
mmu05012                    Pathway                                

Name
Parkinson's disease - Mus musculus (mouse)
Description
Parkinson's disease (PD) is a progressive neurodegenerative movement disorder that results primarily from the death of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Mutations in alpha-synuclein, UCHL1 (a ubiquitin carboxy-terminal hydrolase L1), parkin, DJ1 (a parkin-associated protein involved with oxidative stress), and PINK1 (a putative serine threonine kinase) are known to cause early-onset PD. Mutations or altered expression of these proteins contributes to the damage and subsequent loss of DA neurons through common mechanisms that result in proteasome dysfunction, mitochondrial impairment, and oxidative stress. The demise of DA neurons located in the SNc leads to a drop in the dopaminergic input to the striatum. This results in a reduced activation of the direct pathway and in a disinhibition of the indirect pathway, which is associated with the elevation of adenosine A2A receptor transmission. Such unbalanced activity of the striatal output pathway is at the basis of the motor impairment observed in PD.
Class
Human Diseases; Neurodegenerative diseases
BRITE hierarchy
Pathway map
mmu05012  Parkinson's disease
mmu05012

Ortholog table
Organism
Mus musculus (mouse) [GN:mmu]
Gene
11540  Adora2a; adenosine A2a receptor [KO:K04266]
14680  Gnal; guanine nucleotide binding protein, alpha stimulating, olfactory type [KO:K04633]
13489  Drd2; dopamine receptor D2 [KO:K04145]
14677  Gnai1; guanine nucleotide binding protein (G protein), alpha inhibiting 1 [KO:K04630]
14679  Gnai3; guanine nucleotide binding protein (G protein), alpha inhibiting 3 [KO:K04630]
14678  Gnai2; guanine nucleotide binding protein (G protein), alpha inhibiting 2 [KO:K04630]
224129  Adcy5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
18747  Prkaca; protein kinase, cAMP dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
18749  Prkacb; protein kinase, cAMP dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
13488  Drd1; dopamine receptor D1 [KO:K04144]
22202  Uba1y; ubiquitin-activating enzyme, Chr Y [KO:K03178] [EC:6.2.1.45]
22201  Uba1; ubiquitin-like modifier activating enzyme 1 [KO:K03178] [EC:6.2.1.45]
74153  Uba7; ubiquitin-like modifier activating enzyme 7 [KO:K10698] [EC:6.2.1.45]
22187  Ubb; ubiquitin B [KO:K04551]
22195  Ube2l3; ubiquitin-conjugating enzyme E2L 3 [KO:K04552] [EC:2.3.2.23]
100042355  Gm10705; predicted gene 10705 [KO:K04552] [EC:2.3.2.23]
56791  Ube2l6; ubiquitin-conjugating enzyme E2L 6 [KO:K04553] [EC:2.3.2.23]
140499  Ube2j2; ubiquitin-conjugating enzyme E2J 2 [KO:K04554] [EC:2.3.2.23]
56228  Ube2j1; ubiquitin-conjugating enzyme E2J 1 [KO:K10578] [EC:2.3.2.23]
22213  Ube2g2; ubiquitin-conjugating enzyme E2G 2 [KO:K04555] [EC:2.3.2.23]
67128  Ube2g1; ubiquitin-conjugating enzyme E2G 1 [KO:K10575] [EC:2.3.2.23]
50873  Park2; Parkinson disease (autosomal recessive, juvenile) 2, parkin [KO:K04556] [EC:2.3.2.31]
20617  Snca; synuclein, alpha [KO:K04528]
14763  Gpr37; G protein-coupled receptor 37 [KO:K04243]
18951  Sept5; septin 5 [KO:K04557]
67847  Sncaip; synuclein, alpha interacting protein (synphilin) [KO:K04558]
22223  Uchl1; ubiquitin carboxy-terminal hydrolase L1 [KO:K05611] [EC:3.4.19.12]
21823  Th; tyrosine hydroxylase [KO:K00501] [EC:1.14.16.2]
13162  Slc6a3; solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 [KO:K05036]
110877  Slc18a1; solute carrier family 18 (vesicular monoamine), member 1 [KO:K08155]
214084  Slc18a2; solute carrier family 18 (vesicular monoamine), member 2 [KO:K08155]
17716  ND1; NADH dehydrogenase subunit 1 [KO:K03878] [EC:1.6.5.3]
17717  ND2; NADH dehydrogenase subunit 2 [KO:K03879] [EC:1.6.5.3]
17718  ND3; NADH dehydrogenase subunit 3 [KO:K03880] [EC:1.6.5.3]
17719  ND4; NADH dehydrogenase subunit 4 [KO:K03881] [EC:1.6.5.3]
17720  ND4L; NADH dehydrogenase subunit 4L [KO:K03882] [EC:1.6.5.3]
17721  ND5; NADH dehydrogenase subunit 5 [KO:K03883] [EC:1.6.5.3]
17722  ND6; NADH dehydrogenase subunit 6 [KO:K03884] [EC:1.6.5.3]
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]
100042503  Gm3873; predicted gene 3873 [KO:K03960]
100041273  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 4I1 [KO:K02263]
84682  Cox4i2; cytochrome c oxidase subunit 4I2 [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]
66725  Lrrk2; leucine-rich repeat kinase 2 [KO:K08844] [EC:2.7.11.1]
68943  Pink1; PTEN induced putative kinase 1 [KO:K05688] [EC:2.7.11.1]
57320  Park7; Parkinson disease (autosomal recessive, early onset) 7 [KO:K05687] [EC:3.5.1.124]
64704  Htra2; HtrA serine peptidase 2 [KO:K08669] [EC:3.4.21.108]
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]
105675  Ppif; peptidylprolyl isomerase F (cyclophilin F) [KO:K09565] [EC:5.2.1.8]
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]
Compound
C00002  ATP
C00008  ADP
C00009  Orthophosphate
C00013  Diphosphate
C00020  AMP
C00027  Hydrogen peroxide
C00082  L-Tyrosine
C00212  Adenosine
C00355  3,4-Dihydroxy-L-phenylalanine
C00575  3',5'-Cyclic AMP
C00704  O2.-
C03758  Dopamine
C04599  1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
C07593  Rotenone
C11310  1-Methyl-4-phenylpyridinium
Reference
  Authors
Thomas B, Beal MF
  Title
Parkinson's disease.
  Journal
Hum Mol Genet 16 Spec No. 2:R183-94 (2007)
DOI:10.1093/hmg/ddm159
Reference
  Authors
Lim KL, Lim TM
  Title
Molecular mechanisms of neurodegeneration in Parkinson's disease: clues from Mendelian syndromes.
  Journal
IUBMB Life 55:315-22 (2003)
DOI:10.1080/1521654031000153030
Reference
  Authors
Moore DJ, West AB, Dawson VL, Dawson TM
  Title
Molecular pathophysiology of Parkinson's disease.
  Journal
Annu Rev Neurosci 28:57-87 (2005)
DOI:10.1146/annurev.neuro.28.061604.135718
Reference
  Authors
Abou-Sleiman PM, Muqit MM, Wood NW
  Title
Expanding insights of mitochondrial dysfunction in Parkinson's disease.
  Journal
Nat Rev Neurosci 7:207-19 (2006)
DOI:10.1038/nrn1868
Reference
  Authors
Mizuno Y, Hattori N, Kubo S, Sato S, Nishioka K, Hatano T, Tomiyama H, Funayama M, Machida Y, Mochizuki H
  Title
Progress in the pathogenesis and genetics of Parkinson's disease.
  Journal
Philos Trans R Soc Lond B Biol Sci 363:2215-27 (2008)
DOI:10.1098/rstb.2008.2273
Reference
  Authors
Gandhi S, Wood NW
  Title
Molecular pathogenesis of Parkinson's disease.
  Journal
Hum Mol Genet 14 Spec No. 2:2749-2755 (2005)
DOI:10.1093/hmg/ddi308
Reference
  Authors
Lotharius J, Brundin P
  Title
Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein.
  Journal
Nat Rev Neurosci 3:932-42 (2002)
DOI:10.1038/nrn983
Reference
  Authors
Eriksen JL, Wszolek Z, Petrucelli L
  Title
Molecular pathogenesis of Parkinson disease.
  Journal
Arch Neurol 62:353-7 (2005)
DOI:10.1001/archneur.62.3.353
Reference
  Authors
Sidhu A, Wersinger C, Vernier P
  Title
Does alpha-synuclein modulate dopaminergic synaptic content and tone at the synapse?
  Journal
FASEB J 18:637-47 (2004)
DOI:10.1096/fj.03-1112rev
Reference
  Authors
Sidhu A, Wersinger C, Moussa CE, Vernier P
  Title
The role of alpha-synuclein in both neuroprotection and neurodegeneration.
  Journal
Ann N Y Acad Sci 1035:250-70 (2004)
DOI:10.1196/annals.1332.016
Reference
  Authors
Dauer W, Przedborski S
  Title
Parkinson's disease: mechanisms and models.
  Journal
Neuron 39:889-909 (2003)
DOI:10.1016/S0896-6273(03)00568-3
Reference
  Authors
Feany MB
  Title
New genetic insights into Parkinson's disease.
  Journal
N Engl J Med 351:1937-40 (2004)
DOI:10.1056/NEJMp048263
Reference
  Authors
Beal MF
  Title
Experimental models of Parkinson's disease.
  Journal
Nat Rev Neurosci 2:325-34 (2001)
DOI:10.1038/35072550
Reference
  Authors
Corti O, Hampe C, Darios F, Ibanez P, Ruberg M, Brice A
  Title
Parkinson's disease: from causes to mechanisms.
  Journal
C R Biol 328:131-42 (2005)
DOI:10.1016/j.crvi.2004.10.009
Reference
  Authors
Vila M, Ramonet D, Perier C
  Title
Mitochondrial alterations in Parkinson's disease: new clues.
  Journal
J Neurochem 107:317-28 (2008)
DOI:10.1111/j.1471-4159.2008.05604.x
Reference
  Authors
Vila M, Przedborski S
  Title
Targeting programmed cell death in neurodegenerative diseases.
  Journal
Nat Rev Neurosci 4:365-75 (2003)
DOI:10.1038/nrn1100
Reference
  Authors
Calabresi P, Di Filippo M, Gallina A, Wang Y, Stankowski JN, Picconi B, Dawson VL, Dawson TM
  Title
New synaptic and molecular targets for neuroprotection in Parkinson's disease.
  Journal
Mov Disord 28:51-60 (2013)
DOI:10.1002/mds.25096
Reference
  Authors
Nishi A, Kuroiwa M, Shuto T
  Title
Mechanisms for the modulation of dopamine d(1) receptor signaling in striatal neurons.
  Journal
Front Neuroanat 5:43 (2011)
DOI:10.3389/fnana.2011.00043
Reference
  Authors
Hara M, Fukui R, Hieda E, Kuroiwa M, Bateup HS, Kano T, Greengard P, Nishi A
  Title
Role of adrenoceptors in the regulation of dopamine/DARPP-32 signaling in neostriatal neurons.
  Journal
J Neurochem 113:1046-59 (2010)
DOI:10.1111/j.1471-4159.2010.06668.x
KO pathway
ko05012   

DBGET integrated database retrieval system