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path(MESH:"Parkinsonian Disorders")

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Entity

Name
Parkinsonian Disorders
Namespace
MeSH
Namespace Version
20181007
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/01c9daa61012b37dd0a1bc962521ba51a15b38f1/external/mesh-names.belns

Appears in Networks 2

The Ubiquitin Proteasome System in Neurodegenerative Diseases: Sometimes the Chicken, Sometimes the Egg v1.0.0

Tau protein aggregation is associated with cellular senescence in the brain v1.0.0

In-Edges 13

a(HBP:"alpha-synuclein aggregates") positiveCorrelation path(MESH:"Parkinsonian Disorders") View Subject | View Object

AR-JP is characterized by lack of LBs and alphaSYN aggregates PubMed:14556719

Appears in Networks:

a(MESH:"Inclusion Bodies") negativeCorrelation path(MESH:"Parkinsonian Disorders") View Subject | View Object

Since inclusion bodies are lacking in most cases of AR-JP, it is possible that the ubiquitination of Synphilin by wildtype Parkin plays a role in their formation, by targeting ubiquitinated Synphilin to these bodies and removing it from the cytosol where it can be toxic PubMed:14556719

Appears in Networks:

a(MESH:"Lewy Bodies") negativeCorrelation path(MESH:"Parkinsonian Disorders") View Subject | View Object

Interestingly, with a few exceptions, AR-JP is characterized by a lack of LBs PubMed:14556719

Appears in Networks:

a(MESH:"Lewy Bodies") negativeCorrelation path(MESH:"Parkinsonian Disorders") View Subject | View Object

AR-JP is characterized by lack of LBs and alphaSYN aggregates PubMed:14556719

Appears in Networks:

complex(a(GO:"proteasome complex"), p(HGNC:PRKN)) decreases path(MESH:"Parkinsonian Disorders") View Subject | View Object

Interestingly, mutation at R42 abrogates the binding of Parkin to the proteasome, suggesting that it can cause AR-JP. PubMed:14556719

Appears in Networks:

g(HGNC:PARK7, var("?")) association path(MESH:"Parkinsonian Disorders") View Subject | View Object

Recently discovered mutations in the DJ-1 gene have also been associated with AR-JP (Bonifati et al., 2003). PubMed:14556719

Appears in Networks:

p(HGNC:GPR37) positiveCorrelation path(MESH:"Parkinsonian Disorders") View Subject | View Object

Importantly, the insoluble Pael receptor accumulates in the brains of patients with AR-JP PubMed:14556719

Appears in Networks:
Annotations
MeSH
Brain

p(HGNC:PARK7, var("p.Leu166Pro")) association path(MESH:"Parkinsonian Disorders") View Subject | View Object

Interestingly, one of the DJ-1 mutations that is associated with AR-JP is a point mutation, L166P. PubMed:14556719

Appears in Networks:

p(HGNC:PRKN, var("?")) increases path(MESH:"Parkinsonian Disorders") View Subject | View Object

Various deletion and point mutations in the gene have been found in ~50% of patients with AR-JP (known also as Autosomal Recessive Parkinson’s Disease [ARPD]), one of the most common familial forms of PD (Kitada et al., 1998). PubMed:14556719

Appears in Networks:

p(HGNC:PRKN, var("p.Arg42")) increases path(MESH:"Parkinsonian Disorders") View Subject | View Object

Interestingly, mutation at R42 abrogates the binding of Parkin to the proteasome, suggesting that it can cause AR-JP. PubMed:14556719

Appears in Networks:

p(HGNC:PRKN, var("p.Lys161Asn")) association path(MESH:"Parkinsonian Disorders") View Subject | View Object

An interesting point is that the mutated Parkin species K161N, which is associated with AR-JP, could still ubiquitinate p38, suggesting that it is not loss of function that underlies the human disease (see above). PubMed:14556719

Appears in Networks:

p(HGNC:SNCA, var("?")) association path(MESH:"Parkinsonian Disorders") View Subject | View Object

It is important to note that while mutations in the nonglycosylated 14 kDa form of alphaSYN have been linked to the pathogenesis of PD (see below), to date, they have not been linked with Parkin-associated AR-JP. PubMed:14556719

Appears in Networks:

path(MESH:"Supranuclear Palsy, Progressive") association path(MESH:"Parkinsonian Disorders") View Subject | View Object

PSP is an age-associated tauopathy that clinically manifests as parkinsonism with additional motor abnormalities and cognitive dysfunction (Orr et al., 2017), and is neuropathologically defined by accumulation of four-repeat (4R) tau, NFTs, gliosis and neurodegeneration (Flament et al., 1991) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Supranuclear Palsy, Progressive

Out-Edges 11

path(MESH:"Parkinsonian Disorders") negativeCorrelation a(MESH:"Lewy Bodies") View Subject | View Object

Interestingly, with a few exceptions, AR-JP is characterized by a lack of LBs PubMed:14556719

Appears in Networks:

path(MESH:"Parkinsonian Disorders") negativeCorrelation a(MESH:"Lewy Bodies") View Subject | View Object

AR-JP is characterized by lack of LBs and alphaSYN aggregates PubMed:14556719

Appears in Networks:

path(MESH:"Parkinsonian Disorders") positiveCorrelation p(HGNC:GPR37) View Subject | View Object

Importantly, the insoluble Pael receptor accumulates in the brains of patients with AR-JP PubMed:14556719

Appears in Networks:
Annotations
MeSH
Brain

path(MESH:"Parkinsonian Disorders") association p(HGNC:SNCA, var("?")) View Subject | View Object

It is important to note that while mutations in the nonglycosylated 14 kDa form of alphaSYN have been linked to the pathogenesis of PD (see below), to date, they have not been linked with Parkin-associated AR-JP. PubMed:14556719

Appears in Networks:

path(MESH:"Parkinsonian Disorders") negativeCorrelation a(MESH:"Inclusion Bodies") View Subject | View Object

Since inclusion bodies are lacking in most cases of AR-JP, it is possible that the ubiquitination of Synphilin by wildtype Parkin plays a role in their formation, by targeting ubiquitinated Synphilin to these bodies and removing it from the cytosol where it can be toxic PubMed:14556719

Appears in Networks:

path(MESH:"Parkinsonian Disorders") association p(HGNC:PRKN, var("p.Lys161Asn")) View Subject | View Object

An interesting point is that the mutated Parkin species K161N, which is associated with AR-JP, could still ubiquitinate p38, suggesting that it is not loss of function that underlies the human disease (see above). PubMed:14556719

Appears in Networks:

path(MESH:"Parkinsonian Disorders") positiveCorrelation a(HBP:"alpha-synuclein aggregates") View Subject | View Object

AR-JP is characterized by lack of LBs and alphaSYN aggregates PubMed:14556719

Appears in Networks:

path(MESH:"Parkinsonian Disorders") increases path(HBP:Neurodegeneration) View Subject | View Object

Therefore, patients with AR-JP—who cannot degrade it because of the mutation in the Parkin E3 (see above)—develop neurodegeneration PubMed:14556719

Appears in Networks:
Annotations
MeSH
Parkinsonian Disorders

path(MESH:"Parkinsonian Disorders") association g(HGNC:PARK7, var("?")) View Subject | View Object

Recently discovered mutations in the DJ-1 gene have also been associated with AR-JP (Bonifati et al., 2003). PubMed:14556719

Appears in Networks:

path(MESH:"Parkinsonian Disorders") association p(HGNC:PARK7, var("p.Leu166Pro")) View Subject | View Object

Interestingly, one of the DJ-1 mutations that is associated with AR-JP is a point mutation, L166P. PubMed:14556719

Appears in Networks:

path(MESH:"Parkinsonian Disorders") association path(MESH:"Supranuclear Palsy, Progressive") View Subject | View Object

PSP is an age-associated tauopathy that clinically manifests as parkinsonism with additional motor abnormalities and cognitive dysfunction (Orr et al., 2017), and is neuropathologically defined by accumulation of four-repeat (4R) tau, NFTs, gliosis and neurodegeneration (Flament et al., 1991) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Supranuclear Palsy, Progressive

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BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.