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
Parkinson's disease
mmu05012

All organismsOrtholog 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]
19108  
Prkx; protein kinase, X-linked [KO:K04345] [EC:2.7.11.11]
13488  
Drd1a; dopamine receptor D1A [KO:K04144]
22202  
Uba1y; ubiquitin-activating enzyme, Chr Y [KO:K03178] [EC:6.3.2.19]
22201  
Uba1; ubiquitin-like modifier activating enzyme 1 [KO:K03178] [EC:6.3.2.19]
74153  
Uba7; ubiquitin-like modifier activating enzyme 7 [KO:K10698] [EC:6.3.2.19]
22187  
Ubb; ubiquitin B [KO:K04551]
22195  
Ube2l3; ubiquitin-conjugating enzyme E2L 3 [KO:K04552] [EC:6.3.2.19]
Gm10145; predicted gene 10145 [KO:K04552] [EC:6.3.2.19]
Gm10705; predicted gene 10705 [KO:K04552] [EC:6.3.2.19]
56791  
Ube2l6; ubiquitin-conjugating enzyme E2L 6 [KO:K04553] [EC:6.3.2.19]
140499  
Ube2j2; ubiquitin-conjugating enzyme E2J 2 [KO:K04554] [EC:6.3.2.19]
56228  
Ube2j1; ubiquitin-conjugating enzyme E2J 1 [KO:K10578] [EC:6.3.2.19]
22213  
Ube2g2; ubiquitin-conjugating enzyme E2G 2 [KO:K04555] [EC:6.3.2.19]
67128  
Ube2g1; ubiquitin-conjugating enzyme E2G 1 [KO:K10575] [EC:6.3.2.19]
50873  
Park2; Parkinson disease (autosomal recessive, juvenile) 2, parkin [KO:K04556] [EC:6.3.2.19]
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]
NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1-like; K03957 NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 1 [KO:K03957]
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]
NADH dehydrogenase [ubiquinone] iron-sulfur protein 5-like; K03938 NADH dehydrogenase (ubiquinone) Fe-S protein 5 [KO:K03938]
407785  
Ndufs6; NADH dehydrogenase (ubiquinone) Fe-S protein 6 [KO:K03939]
623286  
Gm6415; predicted pseudogene 6415 [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]
NADH dehydrogenase [ubiquinone] 1 subunit C2-like; K03968 NADH dehydrogenase (ubiquinone) 1 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: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]
cytochrome c oxidase subunit 5B; K02265 cytochrome c oxidase subunit 5b [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]
cytochrome c oxidase subunit 7C; K02272 cytochrome c oxidase subunit 7c [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]
ATP synthase subunit O; K02137 F-type H+-transporting ATPase subunit O [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]
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 [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)
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)
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)
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)
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)
Reference
  Authors
Gandhi S, Wood NW
  Title
Molecular pathogenesis of Parkinson's disease.
  Journal
Hum Mol Genet 14 Spec No. 2:2749-2755 (2005)
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)
Reference
  Authors
Eriksen JL, Wszolek Z, Petrucelli L
  Title
Molecular pathogenesis of Parkinson disease.
  Journal
Arch Neurol 62:353-7 (2005)
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)
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)
Reference
  Authors
Dauer W, Przedborski S
  Title
Parkinson's disease: mechanisms and models.
  Journal
Neuron 39:889-909 (2003)
Reference
  Authors
Feany MB
  Title
New genetic insights into Parkinson's disease.
  Journal
N Engl J Med 351:1937-40 (2004)
Reference
  Authors
Beal MF
  Title
Experimental models of Parkinson's disease.
  Journal
Nat Rev Neurosci 2:325-34 (2001)
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)
Reference
  Authors
Vila M, Ramonet D, Perier C
  Title
Mitochondrial alterations in Parkinson's disease: new clues.
  Journal
J Neurochem 107:317-28 (2008)
Reference
  Authors
Vila M, Przedborski S
  Title
Targeting programmed cell death in neurodegenerative diseases.
  Journal
Nat Rev Neurosci 4:365-75 (2003)
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)
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)
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)
KO pathway
 

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