KEGG PATHWAY: mmu05012

PATHWAY: mmu05012

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 neurons in the substantia nigra. 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. These pathogenic mutations are associated with disease through pathogenic pathways that may commonly lead proteasome dysfunction, mitochondrial impairment, and oxidative stress. Point mutations in alpha-synuclein lead to excessive intracellular accumulation and protofibril formation. Decrease in the amount of soluble alpha-synuclein tends to increase free cytoplasmic dopamine and the formation of reactive oxygen species (ROS). Modification of parkin and UCHL1 are associated with the ubiquitin-proteasome system pathway and may increase proteotoxic stress. Mutations in parkin, DJ1, and PINK1 may alter mitochondiral activity, potentially impairing proteasomal function. Environmental toxins such as N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and rotenone can cause mitochondrial dysfunction and oxidative stress.

Class

Human Diseases; Neurodegenerative diseases

Pathway map

mmu05012

Parkinson's disease

Organism

Mus musculus (mouse) [GN:mmu]

Gene

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]
100040961	Gm10145; predicted gene 10145 [KO:K04552] [EC:6.3.2.19]
100042355	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] [EC:1.6.99.3 1.6.5.3]
54405	Ndufa1; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 1 [KO:K03945] [EC:1.6.99.3 1.6.5.3]
17991	Ndufa2; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 2 [KO:K03946] [EC:1.6.99.3 1.6.5.3]
66091	Ndufa3; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 3 [KO:K03947] [EC:1.6.99.3 1.6.5.3]
17992	Ndufa4; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4 [KO:K03948] [EC:1.6.99.3 1.6.5.3]
407790	Ndufa4l2; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 [KO:K03948] [EC:1.6.99.3 1.6.5.3]
68202	Ndufa5; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 5 [KO:K03949] [EC:1.6.99.3 1.6.5.3]
67130	Ndufa6; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 6 (B14) [KO:K03950] [EC:1.6.99.3 1.6.5.3]
66416	Ndufa7; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 7 (B14.5a) [KO:K03951] [EC:1.6.99.3 1.6.5.3]
68375	Ndufa8; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 8 [KO:K03952] [EC:1.6.99.3 1.6.5.3]
66108	Ndufa9; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 9 [KO:K03953] [EC:1.6.99.3 1.6.5.3]
67273	Ndufa10; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 10 [KO:K03954] [EC:1.6.99.3 1.6.5.3]
70316	Ndufab1; NADH dehydrogenase (ubiquinone) 1, alpha/beta subcomplex, 1 [KO:K03955] [EC:1.6.99.3 1.6.5.3]
239760	Gm4943; predicted pseudogene 4943 [KO:K03956] [EC:1.6.5.3]
69875	Ndufa11; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 11 [KO:K03956] [EC:1.6.5.3]
66414	Ndufa12; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 12 [KO:K11352] [EC:1.6.99.3 1.6.5.3]
67184	Ndufa13; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 13 [KO:K11353] [EC:1.6.99.3 1.6.5.3]
68198	Ndufb2; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 2 [KO:K03958] [EC:1.6.99.3 1.6.5.3]
66495	Ndufb3; NADH dehydrogenase (ubiquinone) 1 beta subcomplex 3 [KO:K03959] [EC:1.6.99.3 1.6.5.3]
68194	Ndufb4; NADH dehydrogenase (ubiquinone) 1 beta subcomplex 4 [KO:K03960] [EC:1.6.99.3 1.6.5.3]
100042503	Gm3873; predicted gene 3873 [KO:K03960] [EC:1.6.99.3 1.6.5.3]
100041273	Gm3244; predicted pseudogene 3244 [KO:K03960] [EC:1.6.99.3 1.6.5.3]
66046	Ndufb5; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 5 [KO:K03961] [EC:1.6.99.3 1.6.5.3]
230075	Ndufb6; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 6 [KO:K03962] [EC:1.6.99.3 1.6.5.3]
66916	Ndufb7; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 7 [KO:K03963] [EC:1.6.99.3 1.6.5.3]
67264	Ndufb8; NADH dehydrogenase (ubiquinone) 1 beta subcomplex 8 [KO:K03964] [EC:1.6.99.3 1.6.5.3]
66218	Ndufb9; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 9 [KO:K03965] [EC:1.6.99.3 1.6.5.3]
68342	Ndufb10; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 10 [KO:K03966] [EC:1.6.99.3 1.6.5.3]
104130	Ndufb11; NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 11 [KO:K11351] [EC:1.6.99.3 1.6.5.3]
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] [EC:1.6.99.3 1.6.5.3]
595136	Ndufs5; NADH dehydrogenase (ubiquinone) Fe-S protein 5 [KO:K03938] [EC:1.6.99.3 1.6.5.3]
100504968	NADH dehydrogenase [ubiquinone] iron-sulfur protein 5-like; K03938 NADH dehydrogenase (ubiquinone) Fe-S protein 5 [EC:1.6.5.3 1.6.99.3] [KO:K03938] [EC:1.6.99.3 1.6.5.3]
407785	Ndufs6; NADH dehydrogenase (ubiquinone) Fe-S protein 6 [KO:K03939] [EC:1.6.99.3 1.6.5.3]
623286	Gm6415; predicted pseudogene 6415 [KO:K03939] [EC:1.6.99.3 1.6.5.3]
631040	NADH dehydrogenase [ubiquinone] iron-sulfur protein 6; K03939 NADH dehydrogenase (ubiquinone) Fe-S protein 6 [EC:1.6.5.3 1.6.99.3] [KO:K03939] [EC:1.6.99.3 1.6.5.3]
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] [EC:1.6.99.3 1.6.5.3]
68197	Ndufc2; NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 2 [KO:K03968] [EC:1.6.99.3 1.6.5.3]
635087	NADH dehydrogenase [ubiquinone] 1 subunit C2-like; K03968 NADH dehydrogenase (ubiquinone) 1 subcomplex unknown 2 [EC:1.6.5.3 1.6.99.3] [KO:K03968] [EC:1.6.99.3 1.6.5.3]
675851	NADH dehydrogenase [ubiquinone] 1 subunit C2-like; K03968 NADH dehydrogenase (ubiquinone) 1 subcomplex unknown 2 [EC:1.6.5.3 1.6.99.3] [KO:K03968] [EC:1.6.99.3 1.6.5.3]
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]
100046079	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]
100048613	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] [EC:3.6.3.14]
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] [EC:3.6.3.14]
66043	Atp5d; ATP synthase, H+ transporting, mitochondrial F1 complex, delta subunit [KO:K02134] [EC:3.6.3.14]
67126	Atp5e; ATP synthase, H+ transporting, mitochondrial F1 complex, epsilon subunit [KO:K02135] [EC:3.6.3.14]
17705	ATP6; ATP synthase F0 subunit 6 [KO:K02126] [EC:3.6.3.14]
11950	Atp5f1; ATP synthase, H+ transporting, mitochondrial F0 complex, subunit B1 [KO:K02127] [EC:3.6.3.14]
11951	Atp5g1; ATP synthase, H+ transporting, mitochondrial F0 complex, subunit c1 (subunit 9) [KO:K02128] [EC:3.6.3.14]
67942	Atp5g2; ATP synthase, H+ transporting, mitochondrial F0 complex, subunit C2 (subunit 9) [KO:K02128] [EC:3.6.3.14]
228033	Atp5g3; ATP synthase, H+ transporting, mitochondrial F0 complex, subunit C3 (subunit 9) [KO:K02128] [EC:3.6.3.14]
71679	Atp5h; ATP synthase, H+ transporting, mitochondrial F0 complex, subunit d [KO:K02138] [EC:3.6.3.14]
28080	Atp5o; ATP synthase, H+ transporting, mitochondrial F1 complex, O subunit [KO:K02137] [EC:3.6.3.14]
100047429	ATP synthase subunit O; K02137 F-type H+-transporting ATPase oligomycin sensitivity conferral protein [EC:3.6.3.14] [KO:K02137] [EC:3.6.3.14]
11957	Atp5j; ATP synthase, H+ transporting, mitochondrial F0 complex, subunit F [KO:K02131] [EC:3.6.3.14]
17706	ATP8; ATP synthase F0 subunit 8 [KO:K02125] [EC:3.6.3.14]
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
C00355	3,4-Dihydroxy-L-phenylalanine
C00704	O2.-
C03758	Dopamine
C04599	1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
C07593	Rotenone
C11310	1-Methyl-4-phenylpyridinium

Reference

PMID:17911161

Authors

Thomas B, Beal MF

Title

Parkinson's disease.

Journal

Hum Mol Genet 16 Spec No. 2:R183-94 (2007)

Reference

PMID:12938733

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

PMID:16022590

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

PMID:16495942

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

PMID:18426756

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

PMID:16278972

Authors

Gandhi S, Wood NW

Title

Molecular pathogenesis of Parkinson's disease.

Journal

Hum Mol Genet 14 Spec No. 2:2749-2755 (2005)

Reference

PMID:12461550

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

PMID:15767499

Authors

Eriksen JL, Wszolek Z, Petrucelli L

Title

Molecular pathogenesis of Parkinson disease.

Journal

Arch Neurol 62:353-7 (2005)

Reference

PMID:15054086

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

PMID:15681812

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

PMID:12971891

Authors

Dauer W, Przedborski S

Title

Parkinson's disease: mechanisms and models.

Journal

Neuron 39:889-909 (2003)

Reference

PMID:15525720

Authors

Feany MB

Title

New genetic insights into Parkinson's disease.

Journal

N Engl J Med 351:1937-40 (2004)

Reference

PMID:11331916

Authors

Beal MF

Title

Experimental models of Parkinson's disease.

Journal

Nat Rev Neurosci 2:325-34 (2001)

Reference

PMID:15770999

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

PMID:18680555

Authors

Vila M, Ramonet D, Perier C

Title

Mitochondrial alterations in Parkinson's disease: new clues.

Journal

J Neurochem 107:317-28 (2008)

Reference

PMID:12728264

Authors

Vila M, Przedborski S

Title

Targeting programmed cell death in neurodegenerative diseases.

Journal

Nat Rev Neurosci 4:365-75 (2003)

KO pathway

ko05012

All links

Pathway (1)   
   BioSystems (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (143)   
   KEGG GENES (143)   
All databases (145)   

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