Entry |
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Name |
Parkinson disease |
Description |
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.
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Category |
Neurodegenerative disease
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Brite |
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
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Pathway |
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Network |
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Element |
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 |
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Gene |
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Env factor |
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Drug |
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]
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Comment |
Disease class: synucleinopathy
Affected region: substantia nigra, putamen, caudate nucleus, hypothalamus
Microscopic lesion: Lewy bodies
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Other DBs |
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Reference |
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Authors |
Cicchetti F, Drouin-Ouellet J, Gross RE |
Title |
Environmental toxins and Parkinson's disease: what have we learned from pesticide-induced animal models? |
Journal |
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Reference |
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Authors |
Hardy J, Lewis P, Revesz T, Lees A, Paisan-Ruiz C |
Title |
The genetics of Parkinson's syndromes: a critical review. |
Journal |
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Reference |
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Authors |
Lesage S, Brice A |
Title |
Parkinson's disease: from monogenic forms to genetic susceptibility factors. |
Journal |
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Reference |
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Authors |
Gitler AD, Chesi A, Geddie ML, Strathearn KE, Hamamichi S, Hill KJ, Caldwell KA, Caldwell GA, Cooper AA, Rochet JC, Lindquist S |
Title |
Alpha-synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity. |
Journal |
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Reference |
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Authors |
Klein C, Lohmann-Hedrich K, Rogaeva E, Schlossmacher MG, Lang AE |
Title |
Deciphering the role of heterozygous mutations in genes associated with parkinsonism. |
Journal |
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Reference |
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Authors |
Dodson MW, Guo M |
Title |
Pink1, Parkin, DJ-1 and mitochondrial dysfunction in Parkinson's disease. |
Journal |
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Reference |
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Authors |
Hague SM, Klaffke S, Bandmann O. |
Title |
Neurodegenerative disorders: Parkinson's disease and Huntington's disease. |
Journal |
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Reference |
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Authors |
Pardo LM, van Duijn CM. |
Title |
In search of genes involved in neurodegenerative disorders. |
Journal |
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Reference |
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Authors |
Eriksen JL, Przedborski S, Petrucelli L |
Title |
Gene dosage and pathogenesis of Parkinson's disease. |
Journal |
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Reference |
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Authors |
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 |
Title |
Distribution, type, and origin of Parkin mutations: review and case studies. |
Journal |
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Reference |
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Authors |
Abou-Sleiman PM, Healy DG, Quinn N, Lees AJ, Wood NW |
Title |
The role of pathogenic DJ-1 mutations in Parkinson's disease. |
Journal |
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Reference |
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Authors |
Le WD, Xu P, Jankovic J, Jiang H, Appel SH, Smith RG, Vassilatis DK |
Title |
Mutations in NR4A2 associated with familial Parkinson disease. |
Journal |
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Reference |
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Authors |
Hernandez DG, Reed X, Singleton AB |
Title |
Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance. |
Journal |
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Reference |
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Authors |
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 |
Title |
CHCHD2 mutations in autosomal dominant late-onset Parkinson's disease: a genome-wide linkage and sequencing study. |
Journal |
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LinkDB |
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