KEGG   DISEASE: Parkinson disease
H00057                      Disease                                

Parkinson disease
Parkinson 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). Both environmental factors and mutations in familial PD-linked genes such as SNCA, Parkin, DJ-1, PINK1 and LRRK2 are associated with PD pathogenesis. These pathogenic mutations and environmental factors are known to cause disease due to oxidative stress, intracellular Ca2+ homeostasis impairment, mitochondrial dysfunctions and altered protein handling compromising key roles of DA neuronal function and survival. The demise of DA neurons located in the SNc leads to a drop in the dopaminergic input to the striatum, which is hypothesized to impede movement by inducing hypo and hyper activity in striatal spiny projection neurons (SPNs) of the direct (dSPNs) and indirect (iSPNs) pathways in the basal ganglia, respectively.
Neurodegenerative disease
Human diseases [BR:br08402]
 Nervous system diseases
  Neurodegenerative diseases
   H00057  Parkinson disease
Human diseases in ICD-11 classification [BR:br08403]
 08 Diseases of the nervous system
  Movement disorders
   8A00  Parkinsonism
    H00057  Parkinson disease
hsa05012  Parkinson disease
hsa05022  Pathways of neurodegeneration - multiple diseases
nt06410  Calcium signaling
nt06412  Unfolded protein response (UPR) signaling
nt06414  Apoptosis
nt06418  Oxidative phosphorylation
nt06419  Microtubule-based transport
nt06420  Ubiquitin-proteasome system
nt06421  Mitophagy
nt06422  Dopamine metabolism
nt06440  Transcription
nt06463  Parkinson disease
N01020  Mutation-inactivated PRKN to Parkin-mediated ubiquitination
N01022  Mutation-inactivated PRKN to Parkin-mediated ubiquitination
N01024  Mutation-inactivated PRKN to Parkin-mediated ubiquitination
N01026  Mutation-inactivated PRKN to Parkin-mediated ubiquitination
N01028  Mutation-inactivated UCHL1 to UCHL1-mediated hydrolysis
N01030  Mutation-caused aberrant SNCA to 26S proteasome-mediated protein degradation
N01031  Mutation-caused aberrant SNCA to VGCC-Ca2+ -apoptotic pathway
N01032  Mutation-inactivated PRKN to mGluR1 signaling pathway
N01033  Mutation-caused aberrant SNCA to ATF6-mediated transcription
N01034  Mutation-caused aberrant SNCA to IRE1a-XBP1 signaling pathway
N01035  Mutation-caused aberrant SNCA to PERK-ATF4 signaling pathway
N01037  Mutation-caused aberrant SNCA to L-DOPA generation
N01039  Mutation-inactivated PRKN to DOPAL generation
N01041  Mutation-caused aberrant SNCA to transport of dopamine
N01042  Mutation-caused aberrant SNCA to electron transfer in Complex I
N01043  Mutation-inactivated PINK1 to electron transfer in Complex I
N01044  MPP+ to electron transfer in Complex I
N01045  Rotenone to electron transfer in Complex I
N01046  Maneb to electron transfer in Complex III
N01047  Mutation-activated LRRK2 to intrinsic apoptotic pathway
N01048  Mutation-inactivated PINK1 to intrinsic apoptotic pathway
N01049  Mutation-inactivated PRKN to intrinsic apoptotic pathway
N01050  Mutation-inactivated PINK1 to intrinsic apoptotic pathway
N01051  Mutation-inactivated DJ1 to intrinsic apoptotic pathway
N01053  Mutation-inactivated PINK1 to PINK1-Parkin-mediated MFN2 degradation
N01054  Mutation-inactivated PRKN to PINK1-Parkin-mediated MFN2 degradation
N01055  Mutation-caused aberrant SNCA to anterograde axonal transport
N01057  Mutation-inactivated DJ1 to FAS-JNK signaling patwhay
N01058  Mutation-inactivated DJ1 to to p53-mediated transcription
N01059  Mutation-inactivated DJ1 to KEAP1-NRF2 signaling pathway
N01402  Manganese to electron transfer in Complex II
N01417  Paraquat to FAS-JNK signaling pathway
(PARK1/PARK4) SNCA (mutation/duplication, triplication) [HSA:6622] [KO:K04528]
(PARK2) Parkin (mutation, genomic rearrangement) [HSA:5071] [KO:K04556]
(PARK5) UCHL1 (mutation) [HSA:7345] [KO:K05611]
(PARK6) PINK1 (mutation) [HSA:65018] [KO:K05688]
(PARK7) DJ1 (mutation) [HSA:11315] [KO:K05687]
(PARK8) LRRK2 (mutation) [HSA:120892] [KO:K08844]
(PARK9) ATP13A2 (mutation) [HSA:23400] [KO:K13526]
(PARK11) GIGYF2 (mutation) [HSA:26058] [KO:K18730]
(PARK13) HTRA2 (mutation) [HSA:27429] [KO:K08669]
(PARK14) PLA2G6 (mutation) [HSA:8398] [KO:K16343]
(PARK15) FBXO7 (mutation) [HSA:25793] [KO:K10293]
(PARK17) VPS35 (mutation) [HSA:55737] [KO:K18468]
(PARK18) EIF4G1 (mutation) [HSA:1981] [KO:K03260]
(PARK19) DNAJC16 (mutation) [HSA:23341] [KO:K09536]
(PARK22) CHCHD2 (mutation) [HSA:51142] [KO:K22758]
NR4A2 (mutation) [HSA:4929] [KO:K08558]
Env factor
MPTP [CPD:C04599]
Rotenone [CPD:C07593]
Maneb [CPD:C15231]
Paraquat [CPD:C14701]
Droxidopa [DR:D01277]
Bromocriptine mesylate [DR:D00780]
Apomorphine hydrochloride [DR:D02004]
Levodopa [DR:D00059]
Carbidopa hydrate and levodopa [DR:D00253]
Carbidopa, levodopa and entacapone [DR:D10293]
Amantadine hydrochloride [DR:D00777]
Ropinirole hydrochloride [DR:D00784]
Pramipexole dihydrochloride [DR:D00559]
Rotigotine [DR:D05768]
Selegiline hydrochloride [DR:D00785]
Rasagiline mesylate [DR:D02562]
Safinamide mesylate [DR:D10191]
Tolcapone [DR:D00786]
Entacapone [DR:D00781]
Opicapone [DR:D10825]
Istradefylline [DR:D04641]
Pimavanserin tartrate [DR:D08969]
Carbidopa [DR:D00558]
Disease class: synucleinopathy
Affected region: substantia nigra, putamen, caudate nucleus, hypothalamus
Microscopic lesion: Lewy bodies
Other DBs
ICD-11: 8A00.0
ICD-10: G20
MeSH: D010300
OMIM: 168600 168601 605543 600116 605909 606324 607060 606693 607688 610297 612953 260300 614203 614251 615528 616710
PMID:19729209 (Env_factor)
Cicchetti F, Drouin-Ouellet J, Gross RE
Environmental toxins and Parkinson's disease: what have we learned from pesticide-induced animal models?
Trends Pharmacol Sci 30:475-83 (2009)
Hardy J, Lewis P, Revesz T, Lees A, Paisan-Ruiz C
The genetics of Parkinson's syndromes: a critical review.
Curr Opin Genet Dev 19:254-65 (2009)
Lesage S, Brice A
Parkinson's disease: from monogenic forms to genetic susceptibility factors.
Hum Mol Genet 18:R48-59 (2009)
PMID:19182805 (PARK9)
Gitler AD, Chesi A, Geddie ML, Strathearn KE, Hamamichi S, Hill KJ, Caldwell KA, Caldwell GA, Cooper AA, Rochet JC, Lindquist S
Alpha-synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity.
Nat Genet 41:308-15 (2009)
PMID:17582365 (PARK2, PARK6, PARK8)
Klein C, Lohmann-Hedrich K, Rogaeva E, Schlossmacher MG, Lang AE
Deciphering the role of heterozygous mutations in genes associated with parkinsonism.
Lancet Neurol 6:652-62 (2007)
PMID:17499497 (PARK2, PARK6, PARK7)
Dodson MW, Guo M
Pink1, Parkin, DJ-1 and mitochondrial dysfunction in Parkinson's disease.
Curr Opin Neurobiol 17:331-7 (2007)
Hague SM, Klaffke S, Bandmann O.
Neurodegenerative disorders: Parkinson's disease and Huntington's disease.
J Neurol Neurosurg Psychiatry 76:1058-63 (2005)
Pardo LM, van Duijn CM.
In search of genes involved in neurodegenerative disorders.
Mutat Res 592:89-101 (2005)
Eriksen JL, Przedborski S, Petrucelli L
Gene dosage and pathogenesis of Parkinson's disease.
Trends Mol Med 11:91-6 (2005)
PMID:15390068 (PARK2)
Hedrich K, Eskelson C, Wilmot B, Marder K, Harris J, Garrels J, Meija-Santana H, Vieregge P, Jacobs H, Bressman SB, Lang AE, Kann M, Abbruzzese G, Martinelli P, Schwinger E, Ozelius LJ, Pramstaller PP, Klein C, Kramer P
Distribution, type, and origin of Parkin mutations: review and case studies.
Mov Disord 19:1146-57 (2004)
Abou-Sleiman PM, Healy DG, Quinn N, Lees AJ, Wood NW
The role of pathogenic DJ-1 mutations in Parkinson's disease.
Ann Neurol 54:283-6 (2003)
PMID:12496759 (NR4A2)
Le WD, Xu P, Jankovic J, Jiang H, Appel SH, Smith RG, Vassilatis DK
Mutations in NR4A2 associated with familial Parkinson disease.
Nat Genet 33:85-9 (2003)
PMID:27090875 (PARK17, PARK18, PARK19)
Hernandez DG, Reed X, Singleton AB
Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance.
J Neurochem 139 Suppl 1:59-74 (2016)
PMID:25662902 (PARK22)
Funayama M, Ohe K, Amo T, Furuya N, Yamaguchi J, Saiki S, Li Y, Ogaki K, Ando M, Yoshino H, Tomiyama H, Nishioka K, Hasegawa K, Saiki H, Satake W, Mogushi K, Sasaki R, Kokubo Y, Kuzuhara S, Toda T, Mizuno Y, Uchiyama Y, Ohno K, Hattori N
CHCHD2 mutations in autosomal dominant late-onset Parkinson's disease: a genome-wide linkage and sequencing study.
Lancet Neurol 14:274-82 (2015)

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