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 神経系の疾患
  運動障害
   8A00  パーキンソン症候群
    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
病因遺伝子 
(PARK1/PARK4) SNCA (duplication, triplication) [HSA:6622] [KO:K04528]
(PARK2) PRKN [HSA:5071] [KO:K04556]
(PARK5) UCHL1 [HSA:7345] [KO:K05611]
(PARK6) PINK1 [HSA:65018] [KO:K05688]
(PARK7) PARK7 [HSA:11315] [KO:K05687]
(PARK8) LRRK2 [HSA:120892] [KO:K08844]
(PARK9) ATP13A2 [HSA:23400] [KO:K13526]
(PARK11) GIGYF2 [HSA:26058] [KO:K18730]
(PARK13) HTRA2 [HSA:27429] [KO:K08669]
(PARK14) PLA2G6 [HSA:8398] [KO:K16343]
(PARK15) FBXO7 [HSA:25793] [KO:K10293]
(PARK17) VPS35 [HSA:55737] [KO:K18468]
(PARK18) EIF4G1 [HSA:1981] [KO:K03260]
(PARK19) DNAJC6 [HSA:9829] [KO:K09526]
(PARK22) CHCHD2 [HSA:51142] [KO:K22758]
(PARK23) VPS13C [HSA:54832] [KO:K19525]
(PARK24) PSAP [HSA:5660] [KO:K12382]
NR4A2 [HSA:4929] [KO:K08558]
MAPT [HSA:4137] [KO:K04380]
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 616840 619491
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    
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    
PMID:12953260 (PARK7)
  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: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:19297401 (PARK1-15)
  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: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
文献    
PMID:26942284 (PARK23)
  著者
Lesage S, Drouet V, Majounie E, Deramecourt V, Jacoupy M, Nicolas A, Cormier-Dequaire F, Hassoun SM, Pujol C, Ciura S, Erpapazoglou Z, Usenko T, Maurage CA, Sahbatou M, Liebau S, Ding J, Bilgic B, Emre M, Erginel-Unaltuna N, Guven G, Tison F, Tranchant C, Vidailhet M, Corvol JC, Krack P, Leutenegger AL, Nalls MA, Hernandez DG, Heutink P, Gibbs JR, Hardy J, Wood NW, Gasser T, Durr A, Deleuze JF, Tazir M, Destee A, Lohmann E, Kabashi E, Singleton A, Corti O, Brice A
  タイトル
Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy.
  雑誌
Am J Hum Genet 98:500-13 (2016)
DOI:10.1016/j.ajhg.2016.01.014
文献    
PMID:32201884 (PARK24)
  著者
Oji Y, Hatano T, Ueno SI, Funayama M, Ishikawa KI, Okuzumi A, Noda S, Sato S, Satake W, Toda T, Li Y, Hino-Takai T, Kakuta S, Tsunemi T, Yoshino H, Nishioka K, Hattori T, Mizutani Y, Mutoh T, Yokochi F, Ichinose Y, Koh K, Shindo K, Takiyama Y, Hamaguchi T, Yamada M, Farrer MJ, Uchiyama Y, Akamatsu W, Wu YR, Matsuda J, Hattori N
  タイトル
Variants in saposin D domain of prosaposin gene linked to Parkinson's disease.
  雑誌
Brain 143:1190-1205 (2020)
DOI:10.1093/brain/awaa064
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:11710889 (MAPT)
  著者
Martin ER, Scott WK, Nance MA, Watts RL, Hubble JP, Koller WC, Lyons K, Pahwa R, Stern MB, Colcher A, Hiner BC, Jankovic J, Ondo WG, Allen FH Jr, Goetz CG, Small GW, Masterman D, Mastaglia F, Laing NG, Stajich JM, Ribble RC, Booze MW, Rogala A, Hauser MA, Zhang F, Gibson RA, Middleton LT, Roses AD, Haines JL, Scott BL, Pericak-Vance MA, Vance JM
  タイトル
Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease.
  雑誌
JAMA 286:2245-50 (2001)
DOI:10.1001/jama.286.18.2245
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