1. Catalog
  2. Nodes
  3. p(MGI:Mapt, pmod(Ph, Ser, 202))

p(MGI:Mapt, pmod(Ph, Ser, 202))

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

Entity

Name
Mapt
Namespace
mgi
Namespace Version
20181021
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/f2f993e599694ab5ce989cc39d789a499f75db99/external/mgi-names.belns

Appears in Networks 2

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

The Spleen Tyrosine Kinase (Syk) Regulates Alzheimer Amyloid-β Production and Tau Hyperphosphorylation* v1.0.0

In-Edges 8

p(MGI:Mapt) hasVariant p(MGI:Mapt, pmod(Ph, Ser, 202)) View Subject | View Object

Appears in Networks:

a(CHEBI:methylglyoxal) increases p(MGI:Mapt, pmod(Ph, Ser, 202)) View Subject | View Object

Here, we found that MG could induce tau hyperphosphorylation at multiple AD-related sites in neuroblastoma 2a cells under maintaining normal cell viability. MG treatment increased the level of advanced glycation end products (AGEs) and the receptor of AGEs (RAGE). PubMed:22798221

Appears in Networks:

p(MGI:Dyrk1a) negativeCorrelation p(MGI:Mapt, pmod(Ph, Ser, 202)) View Subject | View Object

Normalizing the gene dosage of Dyrk1A in the TS mouse rescued the density of senescent cells in the cingulate cortex, hippocampus and septum, prevented cholinergic neuron degeneration, and reduced App expression in the hippocampus, Aß load in the cortex and hippocampus, the expression of phosphorylated tau at the Ser202 residue in the hippocampus and cerebellum and the levels of total tau in the cortex, hippocampus and cerebellum. PubMed:29221819

Appears in Networks:
Annotations
Uberon
cerebellum
Uberon
hippocampal formation
MeSH
Alzheimer Disease
MeSH
Down Syndrome

act(p(MGI:Gsk3b), ma(kin)) directlyIncreases p(MGI:Mapt, pmod(Ph, Ser, 202)) View Subject | View Object

Taken all together, we think that activation of GSK-3b and p38 should be responsible for MG-induced tau hyperphosphorylation. PubMed:22798221

Appears in Networks:

act(p(MGI:Mapk14), ma(kin)) directlyIncreases p(MGI:Mapt, pmod(Ph, Ser, 202)) View Subject | View Object

Taken all together, we think that activation of GSK-3b and p38 should be responsible for MG-induced tau hyperphosphorylation. PubMed:22798221

Appears in Networks:

p(MGI:Syk) positiveCorrelation p(MGI:Mapt, pmod(Ph, Ser, 202)) View Subject | View Object

We further validated Syk as a target-regulating Aβ by showing that pharmacological inhibition of Syk or down-regulation of Syk expression reduces Aβ production and increases the clearance of Aβ across the BBB mimicking (-)-nilvadipine effects. Moreover, treatment of transgenic mice overexpressing Aβ and transgenic Tau P301S mice with a selective Syk inhibitor respectively decreased brain Aβ accumulation and Tau hyperphosphorylation at multiple AD relevant epitopes. PubMed:25331948

Appears in Networks:

a(CHEBI:"2-[[7-(3,4-dimethoxyphenyl)-5-imidazo[1,2-c]pyrimidinyl]amino]-3-pyridinecarboxamide") decreases p(MGI:Mapt, pmod(Ph, Ser, 202)) View Subject | View Object

Interestingly, we also detected a reduction in Tau phosphorylation at PHF-1 (Ser(P)- 396/Ser(P)-404) and CP13 (Ser(P)-202) in epitopes following treatment of Tg Tau P301S mice with BAY61-3606, whereas the RZ3 (Thr(P)-231) Tau epitope was not significantly impacted (Fig. 8) suggesting that Syk inhibition may also control the activity of other downstream kinases involved in Tau hyperphosphorylation PubMed:25331948

Appears in Networks:

a(CHEBI:Nilvadipine) decreases p(MGI:Mapt, pmod(Ph, Ser, 202)) View Subject | View Object

Western blot analyses of brain homogenates show that (-)-nilvadipine significantly reduces Tau phosphorylation in AT8 (phosphorylated Ser-199/Ser-202/Thr-205) and PHF-1 (phosphorylated Ser-396/Ser-404) epitopes (Fig. 3). PubMed:25331948

Appears in Networks:
Annotations
MeSH
Brain

Out-Edges 2

p(MGI:Mapt, pmod(Ph, Ser, 202)) negativeCorrelation p(MGI:Dyrk1a) View Subject | View Object

Normalizing the gene dosage of Dyrk1A in the TS mouse rescued the density of senescent cells in the cingulate cortex, hippocampus and septum, prevented cholinergic neuron degeneration, and reduced App expression in the hippocampus, Aß load in the cortex and hippocampus, the expression of phosphorylated tau at the Ser202 residue in the hippocampus and cerebellum and the levels of total tau in the cortex, hippocampus and cerebellum. PubMed:29221819

Appears in Networks:
Annotations
Uberon
cerebellum
Uberon
hippocampal formation
MeSH
Alzheimer Disease
MeSH
Down Syndrome

p(MGI:Mapt, pmod(Ph, Ser, 202)) positiveCorrelation p(MGI:Syk) View Subject | View Object

We further validated Syk as a target-regulating Aβ by showing that pharmacological inhibition of Syk or down-regulation of Syk expression reduces Aβ production and increases the clearance of Aβ across the BBB mimicking (-)-nilvadipine effects. Moreover, treatment of transgenic mice overexpressing Aβ and transgenic Tau P301S mice with a selective Syk inhibitor respectively decreased brain Aβ accumulation and Tau hyperphosphorylation at multiple AD relevant epitopes. PubMed:25331948

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.