KEGG   DISEASE: パーキンソン病
エントリ  
H00057                                                             

名称    
パーキンソン病
概要    
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.
カテゴリ  
神経変性疾患
階層分類  
ヒト疾患 [BR:jp08402]
 神経系疾患
  神経変性疾患
   H00057  パーキンソン病
ICD-11 による疾患分類 [BR:jp08403]
 08 Diseases of the nervous system
  Movement disorders
   8A00  Parkinsonism
    H00057  パーキンソン病
特定疾患 (難病) [jp08407.html]
 H00057
パスウェイ 
hsa05012  パーキンソン病
関連パスウェイ
hsa05022  Pathways of neurodegeneration - multiple diseases
ネットワーク
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
  エレメント
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
病因遺伝子 
(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]
環境要因  
MPTP [CPD:C04599]
Rotenone [CPD:C07593]
Maneb [CPD:C15231]
Paraquat [CPD:C14701]
治療薬   
ゾニサミド [DR:D00538]
レボドパ [DR:D00059]
ドロキシドパ [DR:D01277]
カベルゴリン [DR:D00987]
アポモルヒネ塩酸塩水和物 [DR:D02004]
レボドパ・カルビドパ水和物 [DR:D00253]
レボドパ・ベンセラジド塩酸塩 [DR:D02135]
カルビドパ・レボドパ・エンタカポン [DR:D10293]
ペルゴリドメシル酸塩 [DR:D00502]
ロピニロール塩酸塩 [DR:D00784]
プラミペキソール塩酸塩水和物 [DR:D00559]
ロチゴチン [DR:D05768]
セレギリン塩酸塩 [DR:D00785]
ラサギリンメシル酸塩 [DR:D02562]
サフィナミドメシル酸塩 [DR:D10191]
エンタカポン [DR:D00781]
オピカポン [DR:D10825]
イストラデフィリン [DR:D04641]
タリペキソール塩酸塩 [DR:D01505]
コメント  
Disease class: synucleinopathy
Affected region: substantia nigra, putamen, caudate nucleus, hypothalamus
Microscopic lesion: Lewy bodies
リンク   
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
文献    
PMID:19729209 (Env_factor)
  著者
Cicchetti F, Drouin-Ouellet J, Gross RE
  タイトル
Environmental toxins and Parkinson's disease: what have we learned from pesticide-induced animal models?
  雑誌
Trends Pharmacol Sci 30:475-83 (2009)
DOI:10.1016/j.tips.2009.06.005
文献    
  著者
Hardy J, Lewis P, Revesz T, Lees A, Paisan-Ruiz C
  タイトル
The genetics of Parkinson's syndromes: a critical review.
  雑誌
Curr Opin Genet Dev 19:254-65 (2009)
DOI:10.1016/j.gde.2009.03.008
文献    
  著者
Lesage S, Brice A
  タイトル
Parkinson's disease: from monogenic forms to genetic susceptibility factors.
  雑誌
Hum Mol Genet 18:R48-59 (2009)
DOI:10.1093/hmg/ddp012
文献    
PMID:19182805 (PARK9)
  著者
Gitler AD, Chesi A, Geddie ML, Strathearn KE, Hamamichi S, Hill KJ, Caldwell KA, Caldwell GA, Cooper AA, Rochet JC, Lindquist S
  タイトル
Alpha-synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity.
  雑誌
Nat Genet 41:308-15 (2009)
DOI:10.1038/ng.300
文献    
PMID:17582365 (PARK2, PARK6, PARK8)
  著者
Klein C, Lohmann-Hedrich K, Rogaeva E, Schlossmacher MG, Lang AE
  タイトル
Deciphering the role of heterozygous mutations in genes associated with parkinsonism.
  雑誌
Lancet Neurol 6:652-62 (2007)
DOI:10.1016/S1474-4422(07)70174-6
文献    
PMID:17499497 (PARK2, PARK6, PARK7)
  著者
Dodson MW, Guo M
  タイトル
Pink1, Parkin, DJ-1 and mitochondrial dysfunction in Parkinson's disease.
  雑誌
Curr Opin Neurobiol 17:331-7 (2007)
DOI:10.1016/j.conb.2007.04.010
文献    
  著者
Hague SM, Klaffke S, Bandmann O.
  タイトル
Neurodegenerative disorders: Parkinson's disease and Huntington's disease.
  雑誌
J Neurol Neurosurg Psychiatry 76:1058-63 (2005)
DOI:10.1136/jnnp.2004.060186
文献    
  著者
Pardo LM, van Duijn CM.
  タイトル
In search of genes involved in neurodegenerative disorders.
  雑誌
Mutat Res 592:89-101 (2005)
DOI:10.1016/j.mrfmmm.2005.06.006
文献    
  著者
Eriksen JL, Przedborski S, Petrucelli L
  タイトル
Gene dosage and pathogenesis of Parkinson's disease.
  雑誌
Trends Mol Med 11:91-6 (2005)
DOI:10.1016/j.molmed.2005.01.001
文献    
PMID:15390068 (PARK2)
  著者
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
  タイトル
Distribution, type, and origin of Parkin mutations: review and case studies.
  雑誌
Mov Disord 19:1146-57 (2004)
DOI:10.1002/mds.20234
文献    
  著者
Abou-Sleiman PM, Healy DG, Quinn N, Lees AJ, Wood NW
  タイトル
The role of pathogenic DJ-1 mutations in Parkinson's disease.
  雑誌
Ann Neurol 54:283-6 (2003)
DOI:10.1002/ana.10675
文献    
PMID:12496759 (NR4A2)
  著者
Le WD, Xu P, Jankovic J, Jiang H, Appel SH, Smith RG, Vassilatis DK
  タイトル
Mutations in NR4A2 associated with familial Parkinson disease.
  雑誌
Nat Genet 33:85-9 (2003)
DOI:10.1038/ng1066
文献    
PMID:27090875 (PARK17, PARK18, PARK19)
  著者
Hernandez DG, Reed X, Singleton AB
  タイトル
Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance.
  雑誌
J Neurochem 139 Suppl 1:59-74 (2016)
DOI:10.1111/jnc.13593
文献    
PMID:25662902 (PARK22)
  著者
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
  タイトル
CHCHD2 mutations in autosomal dominant late-onset Parkinson's disease: a genome-wide linkage and sequencing study.
  雑誌
Lancet Neurol 14:274-82 (2015)
DOI:10.1016/S1474-4422(14)70266-2
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