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p(HGNC:NPEPPS)

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Entity

Name
NPEPPS
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 1

Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease v1.0.0

In-Edges 5

a(MESH:Brain) association act(p(HGNC:NPEPPS)) View Subject | View Object

Aminopeptidases are a group of enzymes that cleave from the N-terminal end of a protein. The family includes alanyl, arginyl, and glutamyl peptidases. Puromycin sensitive aminopeptidase (PSA) is an alanyl peptidase that is responsible for s90% of the aminopeptidase activity in the brain(10). PubMed:24027553

Appears in Networks:
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Text Location
Review

bp(GO:autophagy) association p(HGNC:NPEPPS) View Subject | View Object

PSA has been shown to be involved in the induction of autophagy and specifically the formation of autophagosomes, in a model of overexpressed mutant huntingtin (32). Thus, the in vivo effects of PSA on promoting tau clearance may relate to its ability to modulate the key clearance pathway for abnormal and aggregated proteins (to be described in more detail below). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Huntington Disease
Text Location
Review

p(HGNCGENEFAMILY:Aminopeptidases) hasMember p(HGNC:NPEPPS) View Subject | View Object

Appears in Networks:

p(MGI:Mapt, var("p.P301L")) positiveCorrelation p(HGNC:NPEPPS) View Subject | View Object

Interestingly, PSA was found to be elevated in the cerebellum of these TAUP301L mice (10). The levels of PSA are also higher in human cerebellum compared to cortex in both controls and FTD cases. A slight elevation in PSA was also observed in FTD cortices compared to controls. PubMed:24027553

Appears in Networks:
Annotations
MeSH
Cerebellum
Text Location
Review

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:NPEPPS) View Subject | View Object

Interestingly, PSA was found to be elevated in the cerebellum of these TAUP301L mice (10). The levels of PSA are also higher in human cerebellum compared to cortex in both controls and FTD cases. A slight elevation in PSA was also observed in FTD cortices compared to controls. PubMed:24027553

Appears in Networks:
Annotations
MeSH
Cerebellum
Text Location
Review

Out-Edges 12

act(p(HGNC:NPEPPS)) association a(MESH:Brain) View Subject | View Object

Aminopeptidases are a group of enzymes that cleave from the N-terminal end of a protein. The family includes alanyl, arginyl, and glutamyl peptidases. Puromycin sensitive aminopeptidase (PSA) is an alanyl peptidase that is responsible for s90% of the aminopeptidase activity in the brain(10). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:NPEPPS) positiveCorrelation p(MGI:Mapt, var("p.P301L")) View Subject | View Object

Interestingly, PSA was found to be elevated in the cerebellum of these TAUP301L mice (10). The levels of PSA are also higher in human cerebellum compared to cortex in both controls and FTD cases. A slight elevation in PSA was also observed in FTD cortices compared to controls. PubMed:24027553

Appears in Networks:
Annotations
MeSH
Cerebellum
Text Location
Review

p(HGNC:NPEPPS) decreases p(MGI:Mapt, var("p.P301L")) View Subject | View Object

In addition, a non-functional PSA mutant exacerbated tau pathology in a Drosophila model of tauopathy, while overexpressing PSA ameliorated the tau phenotype and diminished tau levels (10). Overexpressing PSA had a similar effect in the TAUP301L mice, reducing the pathologic phenotype (delaying paralysis, increasing motor neuron density in the spinal cord, decreasing gliosis) and decreasing tau levels (12). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:NPEPPS) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

Interestingly, PSA was found to be elevated in the cerebellum of these TAUP301L mice (10). The levels of PSA are also higher in human cerebellum compared to cortex in both controls and FTD cases. A slight elevation in PSA was also observed in FTD cortices compared to controls. PubMed:24027553

Appears in Networks:
Annotations
MeSH
Cerebellum
Text Location
Review

p(HGNC:NPEPPS) decreases path(MESH:Tauopathies) View Subject | View Object

In addition, a non-functional PSA mutant exacerbated tau pathology in a Drosophila model of tauopathy, while overexpressing PSA ameliorated the tau phenotype and diminished tau levels (10). Overexpressing PSA had a similar effect in the TAUP301L mice, reducing the pathologic phenotype (delaying paralysis, increasing motor neuron density in the spinal cord, decreasing gliosis) and decreasing tau levels (12). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:NPEPPS) decreases p(HGNC:MAPT) View Subject | View Object

In addition, a non-functional PSA mutant exacerbated tau pathology in a Drosophila model of tauopathy, while overexpressing PSA ameliorated the tau phenotype and diminished tau levels (10). Overexpressing PSA had a similar effect in the TAUP301L mice, reducing the pathologic phenotype (delaying paralysis, increasing motor neuron density in the spinal cord, decreasing gliosis) and decreasing tau levels (12). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:NPEPPS) regulates deg(p(HGNC:MAPT)) View Subject | View Object

For example, it has been shown that the isomerase Pin1, which has been implicated in AD (30), had opposite effects on P301L and wild-type tau degradation (31). An alternative explanation for the effects of PSA may be that PSA is indirectly regulating tau degradation. PubMed:24027553

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Text Location
Review

p(HGNC:NPEPPS) decreases path(MESH:Paralysis) View Subject | View Object

In addition, a non-functional PSA mutant exacerbated tau pathology in a Drosophila model of tauopathy, while overexpressing PSA ameliorated the tau phenotype and diminished tau levels (10). Overexpressing PSA had a similar effect in the TAUP301L mice, reducing the pathologic phenotype (delaying paralysis, increasing motor neuron density in the spinal cord, decreasing gliosis) and decreasing tau levels (12). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:NPEPPS) decreases path(MESH:Gliosis) View Subject | View Object

In addition, a non-functional PSA mutant exacerbated tau pathology in a Drosophila model of tauopathy, while overexpressing PSA ameliorated the tau phenotype and diminished tau levels (10). Overexpressing PSA had a similar effect in the TAUP301L mice, reducing the pathologic phenotype (delaying paralysis, increasing motor neuron density in the spinal cord, decreasing gliosis) and decreasing tau levels (12). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:NPEPPS) increases p(HGNC:MAPT, frag("1_?")) View Subject | View Object

PSA was able to cleave recombinant tau in vitro, as well as tau from control human brain (11). However, the data presented in this study suggest that PSA is cleaving tau from both the C- and N-terminal ends, which is not expected from an aminopeptidase. Additionally, other studies failed to demonstrate tau cleavage by PSA (28, 29). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Brain
Text Location
Review

p(HGNC:NPEPPS) increases p(HGNC:MAPT, frag("?_*")) View Subject | View Object

PSA was able to cleave recombinant tau in vitro, as well as tau from control human brain (11). However, the data presented in this study suggest that PSA is cleaving tau from both the C- and N-terminal ends, which is not expected from an aminopeptidase. Additionally, other studies failed to demonstrate tau cleavage by PSA (28, 29). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Brain
Text Location
Review

p(HGNC:NPEPPS) association bp(GO:autophagy) View Subject | View Object

PSA has been shown to be involved in the induction of autophagy and specifically the formation of autophagosomes, in a model of overexpressed mutant huntingtin (32). Thus, the in vivo effects of PSA on promoting tau clearance may relate to its ability to modulate the key clearance pathway for abnormal and aggregated proteins (to be described in more detail below). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Huntington Disease
Text Location
Review

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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.