1. Catalog
  2. Nodes
  3. p(HGNC:MMP9)

p(HGNC:MMP9)

Equivalencies: 0 | Classes: 0 | Children: 0 | Explore

Entity

Name
MMP9
Namespace
hgnc
Namespace Version
20180828
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/1b20f0637c395f8aa89c2e2e342d7b704062c242/external/hgnc-symbols.belns

Appears in Networks 4

Cholinergic system during the progression of Alzheimer’s disease: therapeutic implications v1.0.0

MMP-9 and MMP-2 Contribute to Neuronal Cell Death in iPSC Models of Frontotemporal Dementia with MAPT Mutations v1.0.0

Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing v1.0.0

Clearance of Amyloid Beta and Tau in Alzheimer’s Disease:from Mechanisms to Therapy v1.0.1

In-Edges 25

path(MESH:D000544) increases act(p(HGNC:MMP9)) View Subject | View Object

We found an upregulation of MMP-9 protein levels and activity in both AD and MCI brains, which correlated inversely with cognitive status (Figure 1B) [75]. Since tissue alterations are often reflected in bodily fluids, determination of MMPs in blood, urine and CSF has been recommended as potential biomarkers to act as diagnostic measures to characterize the disease process that occurs in the brain [76–78]. Interestingly, plasma MMP-9 was increased in MCI and AD [77]. PubMed:18986241

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Plasma
MeSH
Cognitive Dysfunction

path(MESH:D003072) positiveCorrelation act(p(HGNC:MMP9)) View Subject | View Object

We found an upregulation of MMP-9 protein levels and activity in both AD and MCI brains, which correlated inversely with cognitive status (Figure 1B) [75]. Since tissue alterations are often reflected in bodily fluids, determination of MMPs in blood, urine and CSF has been recommended as potential biomarkers to act as diagnostic measures to characterize the disease process that occurs in the brain [76–78]. Interestingly, plasma MMP-9 was increased in MCI and AD [77]. PubMed:18986241

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Plasma
MeSH
Cognitive Dysfunction

path(MESH:D060825) increases act(p(HGNC:MMP9)) View Subject | View Object

We found an upregulation of MMP-9 protein levels and activity in both AD and MCI brains, which correlated inversely with cognitive status (Figure 1B) [75]. Since tissue alterations are often reflected in bodily fluids, determination of MMPs in blood, urine and CSF has been recommended as potential biomarkers to act as diagnostic measures to characterize the disease process that occurs in the brain [76–78]. Interestingly, plasma MMP-9 was increased in MCI and AD [77]. PubMed:18986241

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Plasma
MeSH
Cognitive Dysfunction

p(FPLX:ERK) regulates p(HGNC:MMP9) View Subject | View Object

It is known that MMP-9 expression is regulated by ERK (Wang et al., 2006) PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

a(CHEBI:"2-(2-amino-3-methoxyphenyl)chromen-4-one") decreases sec(p(HGNC:MMP9)) View Subject | View Object

Correspondingly, the level and activity of secreted MMP-9 was greatly suppressed in both tau-A152T and MAPT IVS10+16 patient neurons (Figures 4B and 4C), suggesting that MMP-9 expression is regulated by the ERK signaling pathway in cortical neurons PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

a(CHEBI:"2-(2-amino-3-methoxyphenyl)chromen-4-one") decreases act(p(HGNC:MMP9)) View Subject | View Object

Correspondingly, the level and activity of secreted MMP-9 was greatly suppressed in both tau-A152T and MAPT IVS10+16 patient neurons (Figures 4B and 4C), suggesting that MMP-9 expression is regulated by the ERK signaling pathway in cortical neurons PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

bp(GO:"ERK1 and ERK2 cascade") regulates p(HGNC:MMP9) View Subject | View Object

Correspondingly, the level and activity of secreted MMP-9 was greatly suppressed in both tau-A152T and MAPT IVS10+16 patient neurons (Figures 4B and 4C), suggesting that MMP-9 expression is regulated by the ERK signaling pathway in cortical neurons PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases act(p(HGNC:MMP9)) View Subject | View Object

Tau-A152T neurons had >10-fold higher level and activity of secreted MMP-9 than control neurons (Figures 2A and 2B), as did MAPT IVS10+16 neurons to a lesser extent (Figures 2C and 2D) PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases sec(p(HGNC:MMP9)) View Subject | View Object

Tau-A152T neurons had >10-fold higher level and activity of secreted MMP-9 than control neurons (Figures 2A and 2B), as did MAPT IVS10+16 neurons to a lesser extent (Figures 2C and 2D) PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases sec(p(HGNC:MMP9)) View Subject | View Object

The level of secreted MMP-9 and MMP-2 was also increased in cortical neurons derived from a published iPSC line with the tau-A152T mutation (Fong et al., 2013) (Figures 2E and 2F) PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases act(p(HGNC:MMP9)) View Subject | View Object

It is worth noting that the level and activity of secreted MMP-9 in tau- A152T neurons is also substantially higher than that in MAPT IVS10+16 neurons (Figure 2) PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases sec(p(HGNC:MMP9)) View Subject | View Object

It is worth noting that the level and activity of secreted MMP-9 in tau- A152T neurons is also substantially higher than that in MAPT IVS10+16 neurons (Figure 2) PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

g(DBSNP:rs63751011) increases act(p(HGNC:MMP9)) View Subject | View Object

Tau-A152T neurons had >10-fold higher level and activity of secreted MMP-9 than control neurons (Figures 2A and 2B), as did MAPT IVS10+16 neurons to a lesser extent (Figures 2C and 2D) PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
MeSH
Frontotemporal Dementia

g(DBSNP:rs63751011) increases sec(p(HGNC:MMP9)) View Subject | View Object

Tau-A152T neurons had >10-fold higher level and activity of secreted MMP-9 than control neurons (Figures 2A and 2B), as did MAPT IVS10+16 neurons to a lesser extent (Figures 2C and 2D) PubMed:27594586

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(FPLX:ERK, pmod(Ph)) positiveCorrelation act(p(HGNC:MMP9)) View Subject | View Object

We found the level and activity of secreted MMP-9 to correlate well with the extent of ERK phosphorylation (Figure S4A) PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(FPLX:ERK, pmod(Ph)) positiveCorrelation sec(p(HGNC:MMP9)) View Subject | View Object

We found the level and activity of secreted MMP-9 to correlate well with the extent of ERK phosphorylation (Figure S4A) PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HBP:HBP00044, var("p.Ala152Thr")) causesNoChange sec(p(HGNC:MMP9)) View Subject | View Object

Interestingly, the level and activity of secreted MMP-9 in HEK293 cells expressing WT 3R tau and 3R tau-A152T are similar (Figures S4B and S4C) PubMed:27594586

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
HEK293
Confidence
High
MeSH
Frontotemporal Dementia

p(HBP:HBP00044, var("p.Ala152Thr")) causesNoChange act(p(HGNC:MMP9)) View Subject | View Object

Interestingly, the level and activity of secreted MMP-9 in HEK293 cells expressing WT 3R tau and 3R tau-A152T are similar (Figures S4B and S4C) PubMed:27594586

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
HEK293
Confidence
High
MeSH
Frontotemporal Dementia

p(HBP:HBP00045, var("p.Ala152Thr")) increases sec(p(HGNC:MMP9)) View Subject | View Object

However, the secreted MMP-9 level and activity in conditioned medium was significantly higher in cultures of cells expressing tau-A152T than WT tau (Figure 4E) PubMed:27594586

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
HEK293
Confidence
High
MeSH
Frontotemporal Dementia

p(HBP:HBP00045, var("p.Ala152Thr")) increases act(p(HGNC:MMP9)) View Subject | View Object

However, the secreted MMP-9 level and activity in conditioned medium was significantly higher in cultures of cells expressing tau-A152T than WT tau (Figure 4E) PubMed:27594586

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
HEK293
Confidence
High
MeSH
Frontotemporal Dementia

p(HBP:HBP00045, var("p.Ala152Thr")) increases sec(p(HGNC:MMP9)) View Subject | View Object

Taken together, these findings strongly suggest that 4R tau-A152T activates the ERK pathway more strongly, which in turn increases the level and activity of secreted MMP-9. 4R tau-A152T expression (Figures 4E and 4F) but not inhibition of ERK activity (Figures 4B and 4C) also increases the total activity of secreted MMP-2, suggesting that tau-A152T increases the level and activity of secreted MMP-2, likely through an ERK-independent pathway PubMed:27594586

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
HEK293
Confidence
High
MeSH
Frontotemporal Dementia

p(HBP:HBP00045, var("p.Ala152Thr")) increases act(p(HGNC:MMP9)) View Subject | View Object

Taken together, these findings strongly suggest that 4R tau-A152T activates the ERK pathway more strongly, which in turn increases the level and activity of secreted MMP-9. 4R tau-A152T expression (Figures 4E and 4F) but not inhibition of ERK activity (Figures 4B and 4C) also increases the total activity of secreted MMP-2, suggesting that tau-A152T increases the level and activity of secreted MMP-2, likely through an ERK-independent pathway PubMed:27594586

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
HEK293
Confidence
High
MeSH
Frontotemporal Dementia

path(MESH:"Neurodevelopmental Disorders") association act(p(HGNC:MMP9)) View Subject | View Object

Moreover, dysregulation of MMP-9 in the CNS is a cause of neuronal developmental disorders (Reinhard et al., 2015) PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Central Nervous System

a(CHEBI:resveratrol) decreases p(HGNC:MMP9) View Subject | View Object

Interestingly, resver- atrol downregulated RAGE as well as MMP9 — an effect that is related to decreased hippocampal load of Aβ42 (REF.297) . PubMed:30116051

Appears in Networks:

a(CHEBI:"amyloid-beta") increases act(p(HGNC:MMP9)) View Subject | View Object

Among MMPs, MMP-2, -3 and -9, stimulated by Aβ, play important roles in degrading Aβ (Wang et al. 2014) PubMed:29626319

Appears in Networks:

Out-Edges 9

act(p(HGNC:MMP9)) positiveCorrelation path(MESH:D003072) View Subject | View Object

We found an upregulation of MMP-9 protein levels and activity in both AD and MCI brains, which correlated inversely with cognitive status (Figure 1B) [75]. Since tissue alterations are often reflected in bodily fluids, determination of MMPs in blood, urine and CSF has been recommended as potential biomarkers to act as diagnostic measures to characterize the disease process that occurs in the brain [76–78]. Interestingly, plasma MMP-9 was increased in MCI and AD [77]. PubMed:18986241

Appears in Networks:
Annotations
MeSH
Brain
MeSH
Plasma
MeSH
Cognitive Dysfunction

p(HGNC:MMP9) increases p(HGNC:HTT, frag("?")) View Subject | View Object

MMP-9 directly cleaves Huntingtin protein in Huntington’s disease, a progressive neurodegenerative disorder (Miller et al., 2010) PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Huntington Disease

act(p(HGNC:MMP9)) association path(MESH:"Neurodevelopmental Disorders") View Subject | View Object

Moreover, dysregulation of MMP-9 in the CNS is a cause of neuronal developmental disorders (Reinhard et al., 2015) PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Central Nervous System

act(p(HGNC:MMP9)) increases bp(GO:"neuron death") View Subject | View Object

To examine the contributions of increased MMP-9 and MMP-2 to neuronal cell death, we used two compounds that are known to inhibit MMP-9 and MMP-2 activity (catalog #444278 and #444244, Calbiochem). We found that this treatment partially rescued the increased sensitivity to rapamycin and improved survival (Figure 3B) PubMed:27594586

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MMP9) increases bp(GO:"neuron death") View Subject | View Object

MMP-2 and MMP-9 seem to induce cell death directly, since this treatment also increased the TUNEL signal in iPSC-derived neurons (Figures S3D and S3E) PubMed:27594586

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

act(p(HGNC:MMP9)) positiveCorrelation p(FPLX:ERK, pmod(Ph)) View Subject | View Object

We found the level and activity of secreted MMP-9 to correlate well with the extent of ERK phosphorylation (Figure S4A) PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

sec(p(HGNC:MMP9)) positiveCorrelation p(FPLX:ERK, pmod(Ph)) View Subject | View Object

We found the level and activity of secreted MMP-9 to correlate well with the extent of ERK phosphorylation (Figure S4A) PubMed:27594586

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

act(p(HGNC:MMP9)) increases deg(a(CHEBI:"amyloid-beta")) View Subject | View Object

Among MMPs, MMP-2, -3 and -9, stimulated by Aβ, play important roles in degrading Aβ (Wang et al. 2014) PubMed:29626319

Appears in Networks:

p(HGNC:MMP9) increases deg(a(CHEBI:"amyloid-beta")) View Subject | View Object

Exercise training can increase extracellular Aβ clearance in the brains of Tg2576 mice in a dose-dependent manner through up-regulating NEP, IDE, MMP9, LRP1, and HSP70 (Moore et al. 2016) PubMed:29626319

Appears in Networks:

About

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.